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1.
Eur J Clin Microbiol Infect Dis ; 35(3): 443-6, 2016 Mar.
Article in English | MEDLINE | ID: mdl-26740325

ABSTRACT

The purpose of this investigation was to evaluate the patient characteristics, clinical manifestations, microbiology, and modes of treatment of a large cohort of women with acute Bartholin's abscess, from a single medical center. A retrospective study was undertaken of all women diagnosed with acute Bartholin's gland abscess who were admitted to the gynecology department in a university-affiliated tertiary hospital in central Israel from January 2004 to December 2013. A total of 267 women were included in the study. The mean age at diagnosis was 33.5 ± 12.1 years and the mean hospitalization period was 1.4 ± 0.9 days. Pain presented in 152 (56.9 %), swelling in 81 (30.3 %), and fever in 34 (12.7 %). Leukocytosis was detected in 149 (55.8 %). The three main treatment modalities were: antibiotics (75.7 %), abscess drainage (19.1 %), and marsupialization (80.9 %). Bacterial infections were detected in 154 (57.7 %) cultures, Escherichia coli presented in 59 (22.1 %), and Streptococcus species in 27 (10.1 %). The clinical and patient characteristics were similar between women with bacterial and sterile Bartholin's abscesses, though leukocytosis was more prevalent among women with bacterial infections. E. coli was the single most frequent pathogen in cultures of acute Bartholin's abscess. Respiratory tract-associated organisms were also common. This study indicates the polymicrobial spectrum of acute Bartholin's abscess.


Subject(s)
Abscess/diagnosis , Abscess/microbiology , Bartholin's Glands/microbiology , Bartholin's Glands/pathology , Abscess/surgery , Acute Disease , Adult , Bacterial Infections/diagnosis , Bacterial Infections/microbiology , Bacterial Infections/surgery , Cohort Studies , Combined Modality Therapy , Female , Humans , Middle Aged , Recurrence , Retrospective Studies , Risk Factors , Treatment Outcome , Young Adult
2.
Int J Surg ; 20: 75-9, 2015 Aug.
Article in English | MEDLINE | ID: mdl-26079498

ABSTRACT

INTRODUCTION: We investigated parameters associated with recurrence after partial (Le Fort) colpocleisis surgery for severe pelvic organ prolapse (POP) in elderly women. METHODS: A retrospective cohort study included all women who underwent partial colpocleisis in a single tertiary center from February 2007 through July 2013 for stage 3 or 4 triple compartment prolapse. Inclusion criteria were age over 60, sexually inactive, medical comorbidities, increased risk for comprehensive reconstructive pelvic surgery, and refusal or failure to use a pessary as a conservative non-surgical treatment. Exclusion criteria were post-menopausal bleeding, pelvic malignancy, and the desire to preserve coital function. RESULTS: The study group included 47 women of mean age 77.3 ± 8.2 (range 61-91 years). All had medical comorbidities. Fourteen patients (29.8%) had undergone previous hysterectomy. All patients underwent partial colpocleisis and perineorrhaphy. Seven women (14.9%) underwent mid-urethral sling for urinary incontinence. Mean follow-up was 14.8 ± 10.3 months (range, 2-37 months) and mean hospitalization, 3.5 ± 1.5 days (range, 2-9 days). There were no intraoperative complications. Postoperative complications comprised lower urinary tract infection (n = 2). Objective cure (according to vaginal examination) was 80.9% (38/47), and subjective (according to symptoms), 91.5% (43/47). No patient regretted the loss of sexual function. The main reasons for prolapse recurrence were statistically significant longer post-operative vaginal length and wider genital hiatus. CONCLUSIONS: Objective and subjective cure rates of Le Fort colpocleisis for the treatment of severe POP were high with low morbidity. Parameters associated with prolapse recurrence were longer postoperative vaginal length and wider genital hiatus.


Subject(s)
Colpotomy/adverse effects , Pelvic Organ Prolapse/surgery , Aged , Aged, 80 and over , Colpotomy/methods , Female , Humans , Hysterectomy , Middle Aged , Pelvic Organ Prolapse/complications , Pelvic Organ Prolapse/pathology , Postoperative Complications/etiology , Recurrence , Retrospective Studies , Risk Factors , Urinary Incontinence/etiology , Urinary Incontinence/surgery , Vagina/pathology , Vagina/surgery
3.
Acta Radiol ; 49(4): 409-14, 2008 May.
Article in English | MEDLINE | ID: mdl-18415784

ABSTRACT

BACKGROUND: Previous studies that have attempted to evaluate the effectiveness of an iso-osmolar contrast medium (IOCM) iodixanol compared to a low-osmolar contrast medium (LOCM) for contrast procedures show variable results. PURPOSE: To evaluate the nephrotoxicity of the IOCM iodixanol compared to the LOCM iohexol. MATERIAL AND METHODS: We performed a retrospective cohort study from April 2004 to March 2006. All contrast procedures with a pre- and post-exposure creatinine value were evaluated for inclusion. Contrast nephropathy (CN) was defined as post-exposure creatinine elevation of > or = 25% or > 0.5 mg/dl within 7 days of contrast exposure. Cases of iodixanol exposure were matched to control cases of iohexol exposure (1:1) based on age, sex, presence of diabetes, pre-exposure creatinine value, and type of imaging study performed. We matched 397 cases of iodixanol (IOCM) exposure to 397 cases of iohexol (LOCM) exposure. Cases of iodixanol which could not be matched to controls were not included in the analysis. RESULTS: After adjustment for prior creatinine, medications, contrast iodine load, prior exposure to contrast material, heart failure, and hypertension, use of iodixanol did not significantly alter rates of CN compared to iohexol (OR 0.92, 95% CI 0.57-1.46; P = 0.71) or mortality (RR 0.79, 95% CI 0.59-1.06; P = 0.12). CONCLUSION: The use of the IOCM iodixanol was not associated with statistically significant protection against contrast nephropathy or all-cause mortality compared to a matched cohort of patients receiving the LOCM iohexol.


Subject(s)
Iohexol , Triiodobenzoic Acids , Aged , Angiography , Case-Control Studies , Chi-Square Distribution , Contrast Media/adverse effects , Creatinine/urine , Female , Glomerular Filtration Rate , Humans , Iohexol/adverse effects , Kidney Diseases/chemically induced , Kidney Diseases/therapy , Logistic Models , Male , Proportional Hazards Models , Renal Dialysis , Retrospective Studies , Tomography, X-Ray Computed , Triiodobenzoic Acids/adverse effects
4.
Am J Physiol Heart Circ Physiol ; 281(4): H1823-32, 2001 Oct.
Article in English | MEDLINE | ID: mdl-11557577

ABSTRACT

This study was performed to determine whether the fall in myocardial high-energy phosphates (HEP) that occurs during high workstates can be ascribed to either inadequate glycolytic pyruvate generation and conversion to acyl-CoA or limitation of long-chain fatty acid transport into the mitochondria. This was tested by using infusions of either pyruvate or butyrate in anesthetized dogs. Pyruvate was used because it bypasses the glycolytic sequence of reactions, activates pyruvate dehydrogenase, and increases mitochondrial NADH concentration ([NADH(m)]) in isolated myocardium, whereas butyrate enters the mitochondria without need for transport by the rate-limiting, palmitoyl-carnitine transporter. Increasing blood pyruvate from 0.16 +/- 0.016 mM to >3 mM did not alter baseline HEP levels determined with (31)P nuclear magnetic resonance, but caused an increase in the rate-pressure product and a modest increase in myocardial oxygen consumption (MVO(2)). Infusion of dobutamine + dopamine (each 20 microg x kg(-1) x min(-1) iv) increased MVO(2) and caused decreases of myocardial phosphocreatine (PCr)/ATP. Pyruvate partially reversed the decrease of HEP levels produced by catecholamine stimulation, whereas butyrate had no effect. Neither pyruvate nor butyrate caused an increase of MVO(2) during catecholamine infusion. Deoxymyoglobin was not detected by (1)H magnetic resonance spectroscopyy in any group. The data demonstrate that carbon substrate availability to the mitochondria is not the only cause of the reduction of PCr/ATP that occurs at high workstates. Supplemental pyruvate (but not butyrate) attenuated the reduction of PCr/ATP during the high workstates; this may have resulted from direct effects on intermediary metabolism or from other effects such as the free radical scavenging activity of pyruvate.


Subject(s)
Energy Metabolism , Myocardium/metabolism , Phosphates/metabolism , Pyruvic Acid/pharmacokinetics , Adenosine Triphosphate/metabolism , Animals , Biological Availability , Dogs , Magnetic Resonance Spectroscopy , Oxygen Consumption , Phosphocreatine/metabolism
5.
Am J Physiol Heart Circ Physiol ; 280(1): H318-26, 2001 Jan.
Article in English | MEDLINE | ID: mdl-11123247

ABSTRACT

This study was performed to determine the myocyte PO(2) required to sustain normal high-energy phosphate (HEP) levels in the in vivo heart. In 10 normal dogs, myocyte PO(2) values were calculated from the myocardial deoxymyoglobin resonance (Mb-delta) intensity determined with (1)H-NMR spectroscopy during sequential flow reductions produced by a hydraulic occluder that decreased coronary perfusion pressure to approximately 60, 50, and 40 mmHg and, finally, during total occlusion. Myocardial blood flow was measured with microspheres, and HEP levels were determined with (31)P magnetic resonance spectroscopy. During control conditions, Mb-delta was undetectable. Myocardial blood flow was 1.11 +/- 0.06 ml. min(-1). g(-1) during basal conditions and decreased with sequential graded occlusions to 0.78 +/- 0.05, 0.58 +/- 0.03, and 0.38 +/- 0.04 ml. min(-1). g(-1), respectively; blood flow during total occlusion was 0.07 +/- 0.02 ml. min(-1). g(-1). Reductions of blood flow caused progressive increases of Mb-delta, which were associated with decreases of phosphocreatine (PCr), ATP, and the PCr-to-ATP ratio, as well as progressive increases of the P(i)-to-PCr ratio. There was a strong linear correlation between normalized blood flow and Mb-delta (R(2) = 0.89, P < 0.01). Reductions of HEP and PO(2) were also highly correlated (although nonlinearly); with the assumption that myoglobin was 90% saturated with O(2) during basal conditions and 5% saturated during total coronary occlusion, the intracellular PO(2) values for 20% reductions of PCr and ATP were approximately 4. 4 and approximately 0.9 mmHg, respectively. The data indicate that O(2) availability plays an increasing role in regulation of oxidative phosphorylation when mean intracellular PO(2) values fall below 5 mmHg in the in vivo heart.


Subject(s)
Adenosine Triphosphate/metabolism , Coronary Circulation/physiology , Myocardium/metabolism , Oxygen/physiology , Phosphocreatine/metabolism , Adenosine Diphosphate/metabolism , Animals , Blood Pressure , Dogs , Female , Hemodynamics , Magnetic Resonance Spectroscopy , Male , Myocardium/cytology , Myoglobin/metabolism , Oxygen Consumption , Phosphorylation
6.
J Am Coll Cardiol ; 36(1): 282-7, 2000 Jul.
Article in English | MEDLINE | ID: mdl-10898447

ABSTRACT

OBJECTIVES: This study was conducted to test hypotheses stating that: 1) altered signaling for mitochondrial membrane proteins occurs during postinfarction remodeling, and 2) successful myocardial adaptation relates to promotion of specific mitochondrial membrane components. BACKGROUND: Abnormalities in high-energy phosphate content and limitations in adenosine 5'-triphosphate (ATP) synthesis rate occur during the transition to contractile failure from compensatory remodeling after left ventricular infarction. The adenine nucleotide translocator (ANT) and F1-ATPase respectively regulate mitochondrial adenosine 5'-diphosphate (ADP)/ATP exchange and ADP-phosphorylation, which are key components of high-energy phosphate metabolism. METHODS: Steady-state mRNA and protein expression for ANT isoform1 and the beta subunit of the F1-ATPase (betaF1) were analyzed in myocardium remote from the infarction zone eight weeks after left circumflex coronary artery ligation in pigs, demonstrating either successful left ventricular remodeling (LVR, n = 8) or congestive heart failure (CHF, n = 4) as determined by clinical and contractile performance parameters. RESULTS: Substantial reductions in steady-state mRNA expression for ANT1 and betaF1 relative to normal (n = 8) occur in CHF, p < 0.01, but not in LVR. Relative expression for both proteins coordinated with their respective steady-state mRNA levels; CHF at 40% normal, p < 0.05 for ANT and 70% normal for betaF1, p < 0.05. CONCLUSIONS: Maintained signaling for major mitochondrial membrane proteins occurs in association with successful remodeling and adaptation after infarction. Reduced expression of these proteins relates to limited ATP synthesis capacity and high energy phosphate kinetic abnormalities previously demonstrated in CHF. These findings imply that mitochondrial processes participate in myocardial remodeling after infarction.


Subject(s)
Heart Failure/genetics , Mitochondria, Heart/metabolism , Mitochondrial ADP, ATP Translocases/genetics , Proton-Translocating ATPases/genetics , Signal Transduction , Ventricular Remodeling , Animals , Biomarkers , Blotting, Northern , Blotting, Western , Disease Progression , Gene Expression , Heart Failure/metabolism , Heart Failure/physiopathology , Mitochondrial ADP, ATP Translocases/metabolism , Myocardial Contraction , Proton-Translocating ATPases/metabolism , RNA, Messenger/biosynthesis , Swine
7.
J Cardiovasc Magn Reson ; 2(1): 23-32, 2000.
Article in English | MEDLINE | ID: mdl-11545104

ABSTRACT

31P- and 1H-nuclear magnetic resonance spectroscopy (MRS) are powerful tools for studying myocardial energy metabolism. The purpose of this review is to illustrate how these MRS techniques can be used to study complex bioenergetic issues in normal and abnormal in vivo myocardium. The results provide insight into the energetic alterations present in remodeled and hypertrophied myocardium. A detailed understanding of energy metabolism in normal and abnormal myocardium may point the way to improved preventive, diagnostic, and therapeutic modalities for left ventricular dysfunction.


Subject(s)
Hypertrophy, Left Ventricular/metabolism , Magnetic Resonance Spectroscopy , Myocardium/metabolism , Phosphates/metabolism , Coronary Circulation , Humans
8.
Cardiovasc Res ; 42(3): 616-26, 1999 Jun.
Article in English | MEDLINE | ID: mdl-10533601

ABSTRACT

BACKGROUND: High cardiac workloads produced by catecholamine infusion result in loss of myocardial phosphocreatine (PCr) and accumulation of inorganic phosphate (Pi) which are more prominent in heart with left ventricular hypertrophy (LVH) than in normal hearts. Since ischemia can cause changes in phosphorylated compounds similar to those during catecholamine stimulation, this study tested the hypothesis that the exaggerated depletion of PCr and accumulation of Pi during high workloads in LVH is the result of impaired myocyte oxygenation. METHODS AND RESULTS: 31P- and 1H-NMR spectroscopy were used to determine myocardial high energy phosphate levels and myoglobin desaturation, respectively, in eight normal dogs and nine dogs with LVH produced by ascending aortic banding. The mean LV weight/body weight ratio was approximately twice normal in the LVH group. Infusion of dobutamine (15 and 30 micrograms/kg/min), and dobutamine + dopamine (each 20 micrograms/kg/min) caused progressive similar increases in the heart rate x systolic LV pressure product to a maximum of 57.4 +/- 3.3 x 10(3) in normal and 63.9 +/- 2.7 x 10(3) in LVH animals, while myocardial oxygen consumption increased from 0.09 +/- 0.01 to 0.24 +/- 0.04 in normals and from 0.10 +/- 0.02 to 0.25 +/- 0.03 ml/min/g in LVH. PCr/ATP ratios during basal conditions were lower in LVH hearts (1.73 +/- 0.10, 1.61 +/- 0.09 and 1.51 +/- 0.09 in subepicardium, midwall and subendocardium, respectively) as compared with normals (2.24 +/- 0.09, 2.01 +/- 0.08 and 1.89 +/- 0.07; each p < 0.01 normal vs. LVH). Catecholamine infusions caused dose-related decreases in PCr/ATP and appearance of Pi which was more marked in LVH than in normal hearts. 1H-NMR spectroscopy did not detect deoxymyoglobin in either normal or LVH hearts even during the highest workloads. In contrast, occlusion of the anterior descending coronary artery resulted in a large deoxymyoglobin signal. CONCLUSIONS: Increases of cardiac work produced by catecholamine stimulation resulted in greater decreases of PCr and greater increases of Pi in hypertrophied than in normal hearts. These abnormalities were not the result of inadequate intracellular oxygen availability and consequently cannot be ascribed to demand ischemia.


Subject(s)
Cardiotonic Agents , Dobutamine , Hypertrophy, Left Ventricular/metabolism , Myocardium/metabolism , Oxygen Consumption , Adenosine Triphosphate/metabolism , Animals , Coronary Circulation , Dogs , Hypertrophy, Left Ventricular/physiopathology , Magnetic Resonance Spectroscopy , Microspheres , Mitochondria, Heart/metabolism , Phosphocreatine/metabolism
9.
Am J Physiol ; 277(1): H50-7, 1999 07.
Article in English | MEDLINE | ID: mdl-10409181

ABSTRACT

This study tested the hypothesis that the loss of myocardial high-energy phosphates (HEP), which occurs during high cardiac work states [J. Zhang, D. J. Duncker, Y. Xu, Y. Zhang, G. Path, H. Merkle, K. Hendrich, A. H. L. From, R. Bache, and K. Ugurbil. Am. J. Physiol. 268: (Heart Circ. Physiol. 37): H1891-H1905, 1995], is not the result of insufficient intracellular O(2) availability. To evaluate the state of myocardial oxygenation, the proximal histidine signal of deoxymyoglobin (Mb-delta) was determined with (1)H nuclear magnetic resonance spectroscopy (MRS), whereas HEP were examined with (31)P MRS. Normal dogs (n = 11) were studied under basal conditions and during combined infusion of dobutamine and dopamine (20 micrograms . kg(-1). min(-1) iv each), which increased rate-pressure products to >50,000 mmHg. beats. min(-1). Creatine phosphate (CP) was expressed as CP/ATP, and myocardial myoglobin desaturation was normalized to the Mb-delta resonance present during total coronary artery occlusion. This Mb-delta resonance appeared at 71 parts per million downfield from the water resonance. CP/ATP decreased from 2. 22 +/- 0.12 during the basal state to 1.83 +/- 0.09 during the high work state (P < 0.01), whereas DeltaP(i)/CP increased from 0 to 0.21 +/- 0.04 (P < 0.01). Despite these HEP changes, Mb-delta remained undetectable. In contrast, when a coronary stenosis was applied to produce a similar decrease in CP/ATP, Mb-delta reached 0.38 +/- 0.10 of the value present during total coronary occlusion. These data demonstrate that Mb-delta is readily detected in vivo during limitation of coronary blood flow sufficient to cause a decrease of myocardial CP/ATP. However, similar HEP changes that occur at high work states in the absence of coronary occlusion are not associated with a detectable Mb-delta resonance. The findings support the hypothesis that the myocardial HEP changes observed at high work states are not due to inadequate O(2) availability to the mitochondria and emphasize the limitations of interpreting HEP alterations in the absence of knowing the level of myocyte oxygenation.


Subject(s)
Heart/physiology , Oxygen/metabolism , Animals , Coronary Circulation/physiology , Coronary Disease/metabolism , Dogs , Hemodynamics/physiology , Magnetic Resonance Spectroscopy , Myocardium/metabolism , Phosphates/physiology
10.
Ann N Y Acad Sci ; 873: 143-8, 1999 Apr 20.
Article in English | MEDLINE | ID: mdl-10372162

ABSTRACT

Stroke volumes measured by impedance were compared with values obtained by dye dilution and an electromagnetic flowmeter (EMF) on 14 dogs during drug-induced changes in cardiac contraction strength and peripheral resistance changes. Grouping all data for a total of 305 points showed correlations between dye and EMF, dye and impedance, and EMF and impedance of 0.89, 0.68, and 0.72, respectively. Correlations for individual dogs between dye and EMF, dye and impedance, and EMF and impedance ranged from 0.60 to 0.99, -0.39 to 0.96, and -0.26 to 0.89, respectively. These data suggest that the use of impedance cardiac output measurements to make treatment decisions about individual patients could result in serious error.


Subject(s)
Myocardial Contraction/drug effects , Stroke Volume , Animals , Bradykinin/pharmacology , Dogs , Dye Dilution Technique , Electric Impedance , Electromagnetic Phenomena , Isoproterenol/pharmacology , Methoxamine/pharmacology , Propranolol/pharmacology , Rheology , Vascular Resistance/drug effects
11.
Genomics ; 57(3): 451-4, 1999 May 01.
Article in English | MEDLINE | ID: mdl-10329015

ABSTRACT

The Rh blood group system is of clinical importance in blood transfusion and as the cause of hemolytic disease of the newborn. Other than their role as carriers of Rh antigens, very little is known about the function of the Rh polypeptides. As a first step to generate an animal model system in which to study the structure and function of Rh, and to extend the phylogenetic analysis of RH genes, the Rh homologue from Mus musculus was characterized. Comparison of RH from humans and mice revealed 71 and 58% sequence identity at the nucleotide and amino acid levels, respectively. Mouse Rh mRNA encodes a protein which is 1 amino acid longer (418 aa) than that of human (417 aa). Rh protein was detected in mouse erythrocyte membranes and was comparable in size to human Rh. Mouse erythrocytes do not show serologic reactivity with human Rh antibodies, probably because the greatest divergence between the mouse and the human genes was seen in the predicted extracellular loops, while the transmembrane regions were more conserved. The mouse RH locus consists of only one gene, which is important for future genetic manipulation and which also indicates that the RH gene duplication seen in humans has occurred since the mammalian radiation.


Subject(s)
Rh-Hr Blood-Group System/genetics , Amino Acid Sequence , Animals , Base Sequence , Cattle , DNA, Complementary , Humans , Mice , Molecular Sequence Data , Sequence Homology, Amino Acid
12.
Circulation ; 99(7): 942-8, 1999 Feb 23.
Article in English | MEDLINE | ID: mdl-10027819

ABSTRACT

BACKGROUND: Postinfarction left ventricular remodeling (LVR) is associated with reductions in myocardial high-energy phosphate (HEP) levels, which are more severe in animals that develop overt congestive heart failure (CHF). During high work states, further HEP loss occurs, which suggests demand-induced ischemia. This study tested the hypothesis that inadequate myocyte oxygen availability is the basis for these HEP abnormalities. METHODS AND RESULTS: Myocardial infarction was produced by left circumflex coronary artery ligation in swine. Studies were performed in 20 normal animals, 14 animals with compensated LVR, and 9 animals with CHF. Phosphocreatine (PCr)/ATP was determined with 31P NMR and deoxymyoglobin (Mb-delta) with 1H NMR in myocardium remote from the infarct. Basal PCr/ATP tended to be decreased in postinfarct hearts, and this was significant in animals with CHF. Infusion of dobutamine (20 microg x kg-1 x min-1 IV) caused doubling of the rate-pressure product in both normal and LVR hearts and resulted in comparable significant decreases of PCr/ATP in both groups. This decrease in PCr/ATP was not associated with detectable Mb-delta. In CHF hearts, rate-pressure product increased only 40% in response to dobutamine; this attenuated response also was not associated with detectable Mb-delta. CONCLUSIONS: Thus, the decrease of PCr/ATP during dobutamine infusion is not the result of insufficient myocardial oxygen availability. Furthermore, in CHF hearts, the low basal PCr/ATP and the attenuated response to dobutamine occurred in the absence of myocardial hypoxia, indicating that the HEP and contractile abnormalities were not the result of insufficient oxygen availability.


Subject(s)
Myocardial Contraction , Myocardial Infarction/physiopathology , Myocardium/metabolism , Oxygen Consumption , Ventricular Remodeling , Adenosine Triphosphate/metabolism , Animals , Blood Volume , Hemodynamics , Myocardial Infarction/metabolism , Myocardial Infarction/pathology , Myocardium/pathology , Myoglobin/blood , Phosphates/metabolism , Phosphocreatine/metabolism , Swine , Ventricular Function, Left
14.
Am J Physiol ; 273(3 Pt 2): H1452-63, 1997 Sep.
Article in English | MEDLINE | ID: mdl-9321837

ABSTRACT

During moderate reductions of blood flow, the myocardium downregulates contractile function and ATP utilization to result in reduced but stable ATP levels, recovery or stability of (reduced) creatine phosphate (CP), and preservation of myocyte viability. The intent of this study was to determine the influence of the level of ischemic blood flow and the major determinants of myocardial O2 consumption (MVO2) (heart rate and systolic blood pressure) on recovery of CP during prolonged moderate myocardial hypoperfusion. 31P-nuclear magnetic resonance spectroscopy was used to measure CP, ATP, and Pi in the subepicardium (Epi) and subendocardium (Endo) of 13 open-chest dogs. Wall thickening was measured with sonomicrometry. A coronary stenosis reduced mean myocardial blood flow (microspheres) from 1.10 +/- 0.07 to 0.71 +/- 0.06 ml.g-1.min-1 (P < 0.01) and the Endo-to-Epi blood flow ratio from 1.12 +/- 0.07 to 0.59 +/- 0.06 (P < 0.01), and dyskinesis developed. Coronary blood flow and systolic wall thickening did not change significantly during 4 h of hypoperfusion. Epi CP and ATP fell to 80 +/- 4% (P < 0.05) and 93 +/- 3% of control, respectively, at 30 min. Epi CP then recovered to 87 +/- 5% while ATP decreased further to 83 +/- 5% of baseline by the end of the 240-min ischemic period. Endo CP and ATP fell to 53 +/- 4 and 77 +/- 5% of control, respectively, at 30 min; then Endo CP recovered to 85 +/- 6% while ATP decreased further to 68 +/- 6% of baseline at 240 min of hypoperfusion. ADP levels were significantly increased at 30 min but recovered to baseline by 240 min of hypoperfusion. delta Pi/CP increased significantly (Endo > Epi) at the onset of ischemia and then progressively decreased. At 30 min, mild myocardial acidosis was observed in some hearts with variable pH recovery during continuing hypoperfusion. The data demonstrate that variations in blood flow cannot account for the magnitude of the initial fall in CP or for the final extent of recovery. However, the rate at which CP recovered was significantly correlated with the level of blood flow. Variations in the determinants of MVO2 did not account for differences in CP recovery.


Subject(s)
Energy Metabolism , Heart/physiology , Hemodynamics/physiology , Hibernation/physiology , Myocardial Ischemia/physiopathology , Myocardium/metabolism , Adenosine Diphosphate/metabolism , Adenosine Triphosphate/metabolism , Animals , Coronary Circulation , Coronary Disease/physiopathology , Cytosol/metabolism , Dogs , Endocardium/physiology , Endocardium/physiopathology , Heart/physiopathology , Heart Rate , Magnesium/metabolism , Oxygen Consumption , Phosphocreatine/metabolism , Regional Blood Flow , Regression Analysis , Systole , Time Factors
15.
Circulation ; 94(5): 1089-100, 1996 Sep 01.
Article in English | MEDLINE | ID: mdl-8790051

ABSTRACT

BACKGROUND: The underlying mechanisms by which left ventricular remodeling (LVR) leads to congestive heart failure (CHF) are unclear. This study examined the functional and bioenergetic abnormalities associated with postinfarction ventricular remodeling in a new, large animal model. METHODS AND RESULTS: Remodeling was induced by circumflex coronary artery ligation in young pigs. LV mass, volume, ejection fraction (EF), the ratio of scar surface area to LV surface area, and LV wall stresses were calculated from magnetic resonance imaging anatomic data and simultaneously measured LV pressure. Hemodynamics, transmural blood flow, and high-energy phosphates (spatially localized 31P-nuclear magnetic resonance) were measured under basal conditions, during hyperperfusion induced by pharmacological vasodilation with adenosine, and during pyruvate infusion (11 mg/kg per minute IV). Six of 18 animals with coronary ligation developed clinical CHF while the remaining 12 animals had LV dilation (LVR) without CHF. The results were compared with 16 normal animals. EF decreased from 55.9 +/- 5.6% in normals to 34.6 +/- 2.3% in the LVR group (P < .05) and 24.2 +/- 2.8% in the CHF group (P < .05 versus LVR). The infarct scar was larger in CHF hearts than in LVR hearts (P < .05). In normals, LV myocardial creatine phosphate (CP)/ATP ratios were 2.10 +/- 0.10, 2.06 +/- 0.16, and 1.92 +/- 0.12 in subepicardium (EPI), mid myocardium (MID), and subendocardium (ENDO), respectively. In LVR hearts, the corresponding ratios were decreased to 1.99 +/- 0.13, 1.80 +/- 0.14, and 1.57 +/- 0.15 (ENDO P < .05 versus normal). In CHF hearts, CP/ATP ratios were 1.41 +/- 0.14, 1.33 +/- 0.15, and 1.25 +/- 0.15; (P < .05 versus LVR in EPI and MID). The calculated myocardial free ADP levels were significantly increased only in CHF hearts. CONCLUSIONS: Bioenergetic abnormalities in remodeled myocardium are related to the severity of LV dysfunction, which, in turn, is dependent on the severity of the initiating myocardial infarction.


Subject(s)
Energy Metabolism , Myocardial Infarction/physiopathology , Ventricular Function, Left , Adenosine Triphosphate/analysis , Animals , Biopsy , Coronary Circulation , Hemodynamics , Hydrogen-Ion Concentration , Magnesium/analysis , Magnetic Resonance Imaging , Magnetic Resonance Spectroscopy , Myocardial Contraction , Myocardial Infarction/pathology , Pyruvates/pharmacology , Pyruvic Acid , Swine
16.
Circulation ; 92(5): 1274-83, 1995 Sep 01.
Article in English | MEDLINE | ID: mdl-7648676

ABSTRACT

BACKGROUND: This study tested the hypothesis that 31P nuclear magnetic resonance (NMR)-detectable 2-deoxyglucose (2DG) uptake is increased in chronically pressure-overloaded hypertrophied left ventricular myocardium. METHODS AND RESULTS: 31P NMR spectroscopy was used to determine the transmural distribution of high-energy phosphate levels and 2-deoxyglucose-6-phosphate (2DGP) accumulation during intracoronary infusion of 2DG (15 mumol.kg body wt-1.min-1) in eight normal dogs and in eight dogs with severe left ventricular hypertrophy (LVH) produced by ascending aortic banding. The ratio of LV weight to body weight was 8.25 +/- 0.65 g/kg in the LVH group compared with 4.35 +/- 0.11 g/kg in the normal group (P < .01). Myocardial ATP content was decreased by approximately 40% and phosphocreatine (PCr) by approximately 60% in LVH hearts. ATP values were transmurally uniform in LVH and normal hearts, whereas PCr was lower in the subendocardium (Endo) than the subepicardium (Epi) of both groups. The PCr/ATP ratio was lower in LVH hearts (1.72 +/- 0.05, 1.64 +/- 0.07, and 1.53 +/- 0.10 in Epi, midwall, and Endo, respectively) compared with normal hearts (2.36 +/- 0.05, 2.09 +/- 0.06, and 1.96 +/- 0.06; each P < .01 normal versus LVH). Arterial blood levels of glucose, insulin, and free fatty acids were comparable between groups, whereas arterial lactate and norepinephrine levels were significantly higher in the LVH group. 2DG infusion did not affect systemic hemodynamics or myocardial high-energy phosphate or inorganic phosphate levels in either group. At the end of 60 minutes of 2DG infusion, there was no detectable accumulation of 2DGP in the normal hearts. However, seven of the eight LVH hearts showed time-dependent accumulation of 2DGP, which was linearly related to the severity of hypertrophy (r = .90 for subendocardial 2DGP versus LV weight/body weight). A transmural gradient of 2DGP was present, with greatest accumulation in the subendocardium (3.3 +/- 1.6, 5.8 +/- 2.3, and 7.9 +/- 2.2 mumol/g in Epi, midwall, and Endo of the LVH hearts, respectively; P < .05 Epi versus Endo). CONCLUSIONS: The pressure-overloaded hypertrophied left ventricle demonstrated increased accumulation of 2DGP detected with 31P NMR spectroscopy. Accumulation of 2DGP was positively correlated with the degree of hypertrophy and was most marked in the subendocardium.


Subject(s)
Deoxyglucose , Glucose-6-Phosphate/analogs & derivatives , Hypertrophy, Left Ventricular/metabolism , Myocardium/metabolism , Adenosine Triphosphate/metabolism , Animals , Coronary Circulation/physiology , Dogs , Energy Metabolism/physiology , Glucosephosphates/metabolism , Hypertension/complications , Hypertrophy, Left Ventricular/etiology , Magnetic Resonance Spectroscopy , Phosphocreatine/metabolism , Ventricular Pressure/physiology
17.
Am J Physiol ; 268(5 Pt 2): H1891-905, 1995 May.
Article in English | MEDLINE | ID: mdl-7771539

ABSTRACT

The response of myocardial high-energy and inorganic phosphates (HEP and Pi, respectively) and associated changes in myocardial blood flow, lactate uptake, and O2 consumption (MVo2) rates were examined in an open-chest canine model during progressively increasing workloads achieved by catecholamine infusion. HEP and Pi levels (measured with transmurally localized 31P-nuclear magnetic resonance spectroscopy) were unaffected by moderate increases in the level of energy expenditure but were significantly altered by high workloads, especially in the subepicardium. The MVo2 and HEP data from three different protocols that utilized pharmacological augmentation of blood flow demonstrated that the maximal rate of myocardial energy production during inotropic stimulation was dictated by perfusion limitation. This limitation was more severe in the subepicardial layer at the high workloads despite equivalent or even higher increases in blood flow to this layer, reflecting a preferential enhancement of demand in the outer layer by catecholamines. In contrast, under basal conditions, existence of a marginal perfusion limitation was evident in the inner but not in the outer layer.


Subject(s)
Energy Metabolism , Myocardial Contraction , Myocardium/metabolism , Adenosine Triphosphate/metabolism , Animals , Coronary Circulation , Creatine/metabolism , Dogs , Hemodynamics , Hydrogen-Ion Concentration , Lactates/metabolism , Lactic Acid , Magnetic Resonance Spectroscopy , Oxygen Consumption , Phosphates/metabolism , Phosphorus , Reference Values
18.
Am Heart J ; 129(2): 330-42, 1995 Feb.
Article in English | MEDLINE | ID: mdl-7832107

ABSTRACT

To determine the effects of dobutamine stimulation on myocardium distal to a coronary stenosis, transmural spatially localized phosphorus 31 nuclear magnetic resonance measurements of myocardial high-energy phosphate compounds (adenosine triphosphate and phosphocreatine), inorganic phosphate, and blood flow and systolic wall thickening were made in 8 open-chested dogs. Data were collected under (1) control conditions, (2) after the application of a moderate coronary stenosis, (3) during infusion of dobutamine with continuing stenosis, and (4) after the release of the stenosis with continuing dobutamine. Stenosis was associated with concordant reductions of subendocardial blood flow, wall thickening, and high-energy phosphate, and mild elevation of inorganic phosphate; subepicardial measurements were essentially unchanged. During dobutamine infusion, blood flow increased in all myocardial layers. Wall thickening returned to control values in the subendocardium and increased nonsignificantly in the subepicardium. Additional loss of high-energy phosphate occurred only in the subepicardium. The data suggest that improved contractile function associated with dobutamine infusion resulted from the inotropic effects of dobutamine and was made possible by the improved blood flow it produced. The data indicate that measurements of blood flow and contractile function do not reliably predict the transmural myocardial metabolic responses to inotropic perturbations in the hypoperfused heart. Taken together, the present findings yield insights with regard to the interpretation of diagnostic dobutamine stimulation testing with single photon emission tomography, radionuclide angiography, and echocardiography.


Subject(s)
Coronary Circulation/drug effects , Coronary Disease/diagnosis , Dobutamine/pharmacology , Energy Metabolism/drug effects , Myocardial Contraction/drug effects , Myocardium/metabolism , Animals , Coronary Disease/metabolism , Coronary Disease/physiopathology , Disease Models, Animal , Dogs , Exercise Test , Hemodynamics/drug effects , Magnetic Resonance Spectroscopy/instrumentation , Magnetic Resonance Spectroscopy/methods
19.
NMR Biomed ; 8(1): 9-18, 1995 Feb.
Article in English | MEDLINE | ID: mdl-7547185

ABSTRACT

This investigation was performed to determine (i) whether 31P spatially localized 31P NMR spectroscopy could be utilized to determine the transmural distribution of 2-deoxyglucose (2DG) uptake in the in vivo canine heart and (ii) whether transmural 2DG uptake would be affected by a preceding ischemic insult. 2DG was infused and the accumulation of 2-deoxyglucose-6-phosphate (2DGP) was monitored (by means of spatially localized 31P NMR) in control hearts, in pharmacologically hyperperfused hearts, and in hearts subjected to four (5 min) occlusions of the left anterior descending coronary artery. Myocardial blood flow was measured with radioactive microspheres. In control hearts, subendocardial (ENDO) 2DGP contents were significantly higher than those in the subepicardium (EPI) being 3.8 +/- 0.3 and 2.2 +/- 0.2 mumol/g, respectively; the ENDO/EPI ratio of 2DGP was 1.70 +/- 0.21. During hyperperfusion blood flow increased approximately four-fold but 2DGP accumulation was not altered. ATP levels in post-ischemic myocardium were significantly decreased (ENDO more than EPI) and 2DGP accumulation in each layer was increased (p < 0.01 vs control); however, the ENDO/EPI ratio of 2DGP was not altered. 2DG infusion induced a marked elevation of blood insulin and norepinephrine levels. These data demonstrate that in the presence of high blood levels of 2DG and insulin: (i) 2DGP accumulation can be measured in the in vivo canine heart; (ii) in normal hearts 2DG uptake is more pronounced in the inner layers of the left ventricular wall (this transmural 2DG uptake gradient is not due to subendocardial hypoperfusion); and (iii) 2DG uptake is greater in the post-ischemic heart but the ENDO/EPI gradient of 2DG uptake is not altered indicating that the more severe ischemic insult in the subendocardium does not result in a disproportionate increase in 2DG uptake in that region of the myocardium. Although 2DG uptake patterns in this model most probably reflect those of glucose (at comparable glucose and insulin levels), quantitative extrapolations with regard to the rate of glucose uptake are not possible from the present data.


Subject(s)
Deoxyglucose/pharmacokinetics , Glucose-6-Phosphate/analogs & derivatives , Myocardial Ischemia/metabolism , Myocardium/metabolism , Animals , Coronary Vessels/physiology , Deoxyglucose/metabolism , Dogs , Glucosephosphates/metabolism , Glucosephosphates/pharmacokinetics , Hemodynamics/physiology , Magnetic Resonance Spectroscopy/methods , Myocardial Reperfusion , Perfusion , Phosphates/metabolism , Phosphorus Isotopes
20.
Am J Physiol ; 267(3 Pt 2): H894-904, 1994 Sep.
Article in English | MEDLINE | ID: mdl-8092293

ABSTRACT

This study examines the hypothesis that high-energy phosphate (HEP) compound levels in unstimulated in vivo myocardium are defined by 1) the level of perfusion and 2) non-perfusion-dependent metabolic characteristics. This hypothesis was tested by determining 1) the effects of pharmacological hyperperfusion of functioning myocardium on transmural HEP compound distribution, contractile function, and myocardial oxygen consumption rate (MVO2) as well as 2) the effect of KCl cardioplegia on transmural myocardial HEP compound distribution. Creatine phosphate (CP) and ATP were measured across the anterior left ventricular wall using spatially localized 31P-nuclear magnetic resonance (NMR). At baseline, the CP-to-ATP (CP/ATP) ratio was significantly lower in the subendocardium than in the subepicardium. This transmural HEP gradient was abolished by hyperperfusion without significant effects on contractile function or MVO2. Similarly, KCl arrest significantly increased CP and CP/ATP in all myocardial layers, and the transmural gradient of CP/ATP was abolished again. These studies indicate that in present experimental model 1) myocardial performance is not constrained by inadequate perfusion in any myocardial layer although modest oxygen limitation affects the kinetics of oxidative phosphorylation in the inner myocardial layers and 2) in all myocardial layers, submaximal activation of intermediary metabolism and oxidative phosphorylation reactions results in lower steady-state CP and higher ADP levels relative to their respective values when energy expenditure is markedly reduced by KCl arrest.


Subject(s)
Coronary Circulation , Energy Metabolism , Heart Arrest, Induced , Myocardium/metabolism , Phosphates/metabolism , Adenosine Triphosphate/metabolism , Animals , Dogs , Hemodynamics , Magnetic Resonance Spectroscopy , Myocardial Contraction , Oxygen Consumption , Phosphocreatine/metabolism , Potassium Chloride/pharmacology , Tissue Distribution
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