Effects of altering carbohydrate metabolism on energy status and contractile function of vascular smooth muscle.

Substrate-dependent changes in vascular smooth muscle energy metabolism and contractile function were investigated in isolated porcine carotid arteries. In media containing glucose glycogen catabolism accounted for all the estimated high-energy phosphate turnover that occurred in conjunction with contraction induced by 80 mM KCl. However, in glucose-free media glycogen catabolism accounted for only a portion of the estimated ATP utilization in resting and contracting arteries, even though glycogen stores were not depleted. The glycogenolysis and lactate production that ordinarily accompanies contraction was completely inhibited by 5 mM 2-deoxyglucose (2-DG). However, there was no decrease in the high-energy phosphate levels when compared to control resting arteries similarly treated with 2-DG. The results suggest that an endogenous non-carbohydrate source may be an important substrate for energy metabolism. Treatment of arteries with 50 microM iodoacetate (IA) in media containing glucose resulted in a marked reduction of high energy phosphate levels and an accumulation of phosphorylated glycolytic intermediates, as demonstrated by 31P-NMR spectroscopy. In glucose-free media, 50 microM IA had only a slight effect on high-energy phosphate levels, while glycogenolysis proceeded unhindered. With 1 mM IA in glucose-free media, the oxidative metabolism of glycogen was inhibited as evidenced by the depletion of high-energy phosphates and the appearance of sugar phosphates in the 31P-NMR spectra. Thus, the titration of enzyme systems with IA reveals a structural partitioning of carbohydrate metabolism, as suggested by previous studies.

Determination of cardiac output in critically ill patients by dual beam Doppler echocardiography.

Recent technology in Doppler echocardiography has produced a dual beam Doppler instrument that is capable of insonating the total cross-sectional area of the ascending aorta. The purpose of this study was to evaluate the accuracy of this instrument in measuring cardiac output in critically ill patients by comparing results with those of the thermodilution-derived cardiac output. A technically adequate Doppler cardiac output measurement was attained in 71 (91%) of 78 patients. The range of thermodilution-derived cardiac output measurements was from 1.58 to 11.70 liters/min. To maximize thermodilution cardiac output reliability, several measurements were made for each patient. Those patients in whom the difference between the highest and lowest measurement varied by less than 10% from the averaged results were accepted into the 50 patient study. There was significant correlation between dual beam Doppler- and thermodilution-derived cardiac output (r = 0.96, SEE = 0.55 liters/min, p less than 0.0001). This study demonstrates that dual beam Doppler ultrasound is a promising noninvasive method of measuring cardiac output in the critically ill patient.

Adult cardiology and the expanding supply of physicians.

The number of cardiologists can be projected with considerable accuracy into the next century. The total cardiology pool of physicians will increase until the year 2015 at which time those entering and leaving the pool will come into equilibrium. At that time the ratio of active cardiologists to the population will have greatly increased. This nation's future need for cardiologists is difficult to assess with any degree of precision. Therefore, this is the time for updating practice profile studies. Such studies today could be formulated in a manner to provide more detailed information on the cardiologist's daily activities. In addition, a data base developed through methodology such as the consensus formation approach must be developed and updated on a periodic basis. Through such analyses it will be possible to quantitate the future needs of cardiovascular manpower.

Findings on routine right heart catheterization in patients with suspected coronary artery disease.

Whether catheterization of the right heart should be performed routinely in all patients undergoing coronary angiography for assessment of coronary artery disease is controversial. To objectively assess the utility of routine right heart catheterization, hemodynamic data from 2,178 patients studied for angina having no signs, symptoms, or history of congestive heart failure were analyzed retrospectively. The salient results are as follows: 0.9% patients had unsuspected mitral valve gradients greater than or equal to 5 mm Hg; 0.4% had occult left-to-right shunts; 1% had pulmonary hypertension (pulmonary artery systolic pressure greater than or equal to 40 mm Hg) not attributable to an elevated mean pulmonary capillary wedge pressure (PCWP); 4.8% had PCWP greater than or equal to 18 mm Hg; 6% had cardiac indexes less than or equal to 2.0 L/min/m2, suggesting subclinical left ventricular failure. Overall, 14.5% of patients had at least one abnormal right-sided hemodynamic variable revealed by right heart catheterization. The frequency of abnormalities increased with increasing Canadian Cardiovascular Society grade of angina. Ten percent of grade 1, 14% of grade 2, 15% of grade 3, and 19% of patient 4 patients had at least one abnormality (phi 2 test, p less than or equal to 0.005). It is concluded that the right heart catheterization adds an important dimension to the diagnosis and treatment of patients undergoing coronary angiography for assessment of coronary artery disease and might significantly influence subsequent patient management.

Protein-bound homocyst(e)ine. A possible risk factor for coronary artery disease.

The development of atherosclerotic changes and thromboembolism are common features in homocystinurics. Hence, we postulate a positive correlation between the level of homocyst(e)ine in the blood and the occurrence of coronary artery disease. Homocysteine is found either as free homocystine, cysteine-homocysteine mixed disulfide, or protein-bound homocyst(e)ine. In nonhomocystinuric subjects, most homocysteine molecules are detectable in the protein-bound form. Thus, protein-bound homocyst(e)ine in stored plasma which reflected total plasma homocyst(e)ine was determined in 241 patients with coronary artery disease (173 males and 68 females). The mean +/- SD total plasma homocyst(e)ine was 5.41 +/- 1.62 nmol/ml in male patients, 4.37 +/- 1.09 nmol/ml in male controls, 5.66 +/- 1.93 nmol/ml in female patients, and 4.16 +/- 1.62 nmol/ml in female controls. The differences between the patients with coronary artery disease and the controls were statistically significant (P less than 0.0005).

31P-nuclear magnetic resonance analysis of extracts of vascular smooth muscle.

31P-nuclear magnetic resonance spectroscopy was used to assess phosphate metabolites in perchloric acid extracts of rabbit aorta. In addition to the high energy phosphates, several other phosphorus compounds were detected and quantified. Most notable was the presence of a prominent phosphomonoester compound appearing at a chemical shift of 3.86 delta. This compound constituted 26% of the total extractable tissue phosphorus and is tentatively identified as ribose-5-phosphate, a pentose phosphate pathway intermediate. While ATP and phosphocreatine did not change during glucose and oxygen deprivation or during prolonged muscle contraction, the 3.86 delta phosphate decreased significantly. Furthermore, theophylline, an agent that increases intracellular cAMP, also decreased the level of the 3.86 delta phosphate. These results are consistent with the concept that intermediate metabolism sustains high energy phosphate pools in vascular smooth muscle in the steady state under various conditions. The pentose phosphate pathway may play an important role in vascular smooth muscle metabolism.

Relation of ventricular premature beats to underlying heart disease.

The relation between ventricular premature beats (VPBs) and physiologic disease was investigated in 305 patients who had 24-hour Holter monitoring tests, cardiac catheterization and angiography. Both frequency and Lown class of VPBs were measured. Analyses showed that occurrence of VPBs at an average frequency of more than 2 per hour or occurrence of complex VPBs (Lown class greater than 2) have the highest association with the presence and severity of cardiac disease. Using these criteria, VPB severity was then compared with extent of ventricular wall motion abnormality (right anterior oblique projection segments), ejection fraction, end-diastolic pressure, category of disease (normal, coronary artery disease [CAD], valvular heart disease, dilated cardiomyopathy), age and severity of CAD (major coronary arteries with greater than 75% diameter reduction). Severe VPBs defined either by complexity or frequency were significantly correlated with extent of wall motion abnormality, ejection fraction, category of disease and age. Severe VPBs were not significantly correlated with end-diastolic pressure or severity of CAD. Discriminant analysis then showed that in addition to wall motion abnormality and ejection fraction, category of disease and age are independently correlated with VPB severity.

Coronary artery disease: detection by phase analysis of rest/exercise radionuclide angiocardiograms.

Thirty-six patients with chest pain but no myocardial infarction or conduction defects and 4 volunteers (3 normals and 1 with asymptomatic aortic insufficiency) underwent radionuclide angiocardiography. Phase analysis was performed and the standard deviation (SD) ("spread") and skewness ("asymmetry") of the left ventricular (LV) phase histogram determined at rest and during maximum exercise. The SD of the LV phase histogram was of no value; however, when -0.1 was taken as the upper limit of normal skewness at maximum exercise, skewness was equally as sensitive as conventional criteria for coronary artery disease (CAD) and also more specific. The authors conclude that LV histogram skewness during maximum exercise may be superior to conventional criteria for detection of CAD with rest/exercise radionuclide angiocardiograms.

Normal electrophysiological findings in a patient with symptomatic intermittent advanced atrioventricular block.

This report describes an otherwise healthy young woman who presented with syncope during episodes of advanced atrioventricular (AV) block. The His bundle recordings during normal sinus rhythm and atrial and ventricular pacing were normal. Carotid sinus massage produced no abnormality. Subsequently, the patient received a permanent pacemaker and has been free of symptoms. Intermittent advanced AV block has been observed on follow-up electrocardiograms. This unique case demonstrates a potential limitation of routine electrophysiologic investigation.

Significance of ventricular tachycardia in idiopathic dilated cardiomyopathy: observations in 35 patients.

To evaluate the significance of ventricular tachycardia (VT) in idiopathic dilated cardiomyopathy (IDC), 35 consecutive patients seen between 1976 and 1980 were studied. The criteria for diagnosis of IDC were based on clinical, laboratory, and cardiac catheterization findings. All patients had right and left heart catheterization, left ventriculography, and coronary cineangiography. Long-term ambulatory electrocardiograms (Holter) were obtained in all patients at the time of diagnosis. There were 24 male and 11 female patients aged 22 to 72 years (mean +/- standard deviation [SD]51 +/- 12). Frequent ventricular premature beats (VPB) (30/h) were observed in 29 patients (83%): complex VPB (Lown grades 3, 4, and 5) in 93% and simple VPB in 7%. Twenty-one patients (60%) had nonsustained VT consisting of 3 to 46 beats (8 +/- 5) with rates from 75 to 210/min. No difference between patients with and those without VT was observed in regard to the presenting symptoms, functional classification, electrocardiographic findings, heart size on chest X-ray, and the hemodynamic measurements including cardiac index, left ventricular end-diastolic pressure, and ejection fraction. Patients with VT were older (p less than 0.05). Follow-up observation from 4 to 74 months (34 +/- 17) showed that 2 patients died suddenly (1 with and 1 without previous VT), a third patient died from intractable congestive heart failure, and the fourth from sepsis. It is concluded that (1) the incidence of ventricular arrhythmias in IDC is high, (2) VT is frequent and tends to occur in the nonsustained form, and (3) there is no correlation between VT and the clinical and hemodynamic findings. VT does not appear to predict prognosis during a relatively short follow-up period in patients with IDC.

Sequence and timing of ventricular wall motion in patients with bundle branch block. Assessment by radionuclide cineangiography.

We determined the sequence and timing of inward ventricular wall motion by least-square phase analysis of radionuclide cineangiograms in 10 patients with left bundle branch block (LBBB), five patients with right bundle branch block (RBBB) and 11 patients with normal conduction. All LBBB and RBBB patients had normal coronary arteries and no segmental wall motion abnormalities. The left ventricle (LV) was divided into eight segments and the right ventricle (RV) into three; sequence and timing were scored by three observers. In normal subjects, wall motion begins in either or both ventricles and ends in the LV or both ventricles. In patients with LBBB it begins in the RV and ends in the LV; in patients with RBBB is begins in the LV and ends in the RV or both ventricles. The intraventricular wall motion is also altered in the ventricle ipsilateral to a bundle branch block. In LBBB, the mean time of onset of LV wall motion is delayed 1.9 frames (38 msec), whereas RV wall motion is normal. In RBBB, the onset of RV wall motion is delayed 1.3 frames (26 msec), whereas LV wall motion is not delayed.

Noninvasive identification of initial site of abnormal ventricular activation by least-square phase analysis of radionuclide cineangiograms.

Least-square phase analysis (LSPA) of radionuclide cineangiograms demonstrates the sequence of onset of inward ventricular movement noninvasively. To validate the method and explore its ability to identify abnormal initial sites of ventricular activation, LSPA was applied to 14 patients with pacemakers (one with electrodes in two locations) (group 1) and three patients with recurrent ventricular tachycardia (VT) (group 2) who had undergone electrophysiologic endocardial mapping. The segment in which the site of initial ventricular activation was located was correctly identified in 13 of 15 paced studies and in two of three group 2 patients during VT. Pacing increased the duration of spread of onset of inward ventricular movement, and the duration of spread of onset correlated well with the duration of the QRS (r = 0.80). The sequence of onset of inward ventricular movement during VT was similar to the sequence of depolarization in all three group 2 patients. These preliminary results suggest that the sequence of onset of ventricular contraction as depicted by LSPA is a valid representation of the actual contraction sequence and that LSPA or radionuclide cineangiography correctly identifies abnormal sites of initial ventricular activation.

The effect of left ventricular aneurysmectomy on the electrocardiogram: a study of 77 patients and review of the literature.

UNLABELLED: Electrocardiograms (ECGs) were reviewed in patients undergoing left ventricular aneurysmectomy. Post-operatively, significant decreases were noted in ST segment elevation (p less than 0.001) and anterior (p less than 0.03) and inferior R wave heights (p less than 0.002). In addition, abnormal Q waves disappeared in 50% of patients. Comparison of ECG changes between survivors and patients dying of cardiac related events revealed that patients with a preoperative axis of greater than or equal to 60 degrees, postoperative leftward axis shifts and a marked decrease in ST segment elevation and/or R wave height had significantly higher mortality. CONCLUSION: 1) Left ventricular aneurysmectomy affects ventricular depolarization as evidenced by a significant loss of R wave height and changes in infarct pattern; 2) LVA affects ventricular repolarization as evidenced by a significant decrease in ST elevation; 3) the ventricular aneurysm appears to contain "viable muscle" that contributes to ventricular depolarization and remains partially depolarized during diastole; and 4) there are prognostic electrocardiographic parameters, which correlate with mortality during postoperative follow-up.

Diaphragmatic left ventricular aneurysm. Clinical features, surgical treatment, and long-term follow-up in 22 patients.

Although the formation of a left ventricular aneurysm (LVA) is a common and well-recognized complication of myocardial infarction (MI), diaphragmatic LVA is a rare clinical entity. Of 354 consecutive patients who underwent LVA resection, we describe the clinical features and surgical results of 22 patients (6%) with diaphragmatic LVA. All patients had a history of MI. The principal clinical indication for surgery was heart failure in nine patients, angina pectoris in ten patients, and recurrent ventricular tachycardia unresponsive to medical therapy in three patients. A ventricular septal defect was present in two patients, and moderate to severe mitral regurgitation was present in four patients. Three of the four surgical deaths (operative mortality, 18%) occurred in patients with mitral regurgitation or with ventricular septal defect. Eleven patients are alive at a mean follow-up of 40 months. Six of them are asymptomatic and two have angina at a higher level of physical activity than before surgery. Notable differences exist in the clinical presentation and surgical findings between patients with diaphragmatic and anterior LVA.

Mortality related to cardiac catheterization and angiography.

During a 14-month period, 75 deaths occurring in relation to 53,581 cardiac catheterizations were consecutively and prospectively reported to the Registry Committee of the Society for Cardiac Angiography. Three of the patients died several days after their catheterization from an unrelated cause and are excluded from this analysis. There were 21 patients (group I) who arrived at the laboratory in extremis and whose deaths were expected irrespective of the catheterization. Most of these patients suffered from recent myocardial infarctions and cardiogenic shock, or had complex congenital malformations. In 35 patients (group II), a cardiovascular complication occurring during the catheterization resulted in death. In 16 patients (group III) catheterization seemed uneventful, but death occurred suddenly 10 min to 10 h after the procedure. Of these 16 patients, eight had left main coronary artery obstruction greater than or equal to 90%, five had three-vessel disease all with 90% obstructions, one had 2-vessel disease both with 90% obstructions, and who had critical aortic stenosis. The 51 unexpected deaths (groups II and III) were considered to be causally related to the procedure, a mortality rate of 0.10%. Subsets with an increased mortality rate (M), were patients with: a) left main disease greater than 50% (M = 0.94%); b) ejection fraction less than 30% (M = 0.54%); c) NYHA class III or IV (m = 0.24%); d) age over 60 years (M = 0.23%); or e) three-vessel disease (M = 0.13%). In conclusion, catheterization related mortality occurs mostly in patients with far advanced cardiac disease. Nearly 1/3 of the unexpected deaths occurred suddenly after a seemingly uneventful procedure. Close monitoring after catheterization of patients with similar characteristics (left main disease greater than or equal to 90%, or three-vessel disease all greater than or equal to 90%) might disclose avenues for reducing mortality occurring after catheterization.