The evaluation of a precordial ECG BELT: technologist satisfaction and accuracy of recording.

The standard method for performing electrocardiogram (ECG) recordings presents a challenge to technicians because of the need to correctly position the individual precordial electrodes according to 6 bony thoracic landmarks. A proposed new method using a 6-lead ECG BELT for precordial application was compared to the standard method to determine the level of agreement among automated interpretations. A comparison of automated interpretations from repeat standard recordings served as the control. Results indicate that BELT and standard automated interpretations disagreed significantly more frequently than repeat standard recording automated interpretations of the cardiac rhythm. The BELT's most obvious weakness was the inability to obtain a recording with a stable ECG baseline, triggering automated detection of "baseline artifact or wander," and requiring a repeat recording. These findings suggest that the ECG BELT is not adequate for clinical application in its current form.

Normal myocardial function in severe right ventricular volume overload hypertrophy.

Severe left ventricular volume overloading causes myocardial and cellular contractile dysfunction. Whether this is also true for severe right ventricular volume overloading was unknown. We therefore created severe tricuspid regurgitation percutaneously in seven dogs and then observed them for 3.5-4.0 yr. All five surviving operated dogs had severe tricuspid regurgitation and right heart failure, including massive ascites, but they did not have left heart failure. Right ventricular cardiocytes were isolated from these and from normal dogs, and sarcomere mechanics were assessed via laser diffraction. Right ventricular cardiocytes from the tricuspid regurgitation dogs were 20% longer than control cells, but neither the extent (0.171 +/- 0.005 microm) nor the velocity (2.92 +/- 0.12 microm/s) of sarcomere shortening differed from controls (0.179 +/- 0.005 microm and 3.09 +/- 0.11 microm/s, respectively). Thus, despite massive tricuspid regurgitation causing overt right heart failure, intrinsic right ventricular contractile function was normal. This finding for the severely volume-overloaded right ventricle stands in distinct contrast to our finding for the left ventricle severely volume overloaded by mitral regurgitation, wherein intrinsic contractile function is depressed.

Interaction between transient metabolically mediated dilatation and pressure induced constriction in the canine coronary artery.

This study explored the interaction between metabolically mediated vasodilatation (ventricular extra-activation) and pressure induced vasoconstriction (transient augmentation of aortic diastolic pressure). Eight dogs having formalin-induced heart block were chronically instrumented with aortic and left ventricular catheters and an electromagnetic flow probe on the left circumflex coronary artery. At a heart rate of 60 beats/min a single ventricular extra-activation introduced at 200 ms after the normal paced beat resulted in a 13 +/- 1% decrease in diastolic coronary vascular resistance index (DCVRI) in the first response beat (D1) and a persistent vasodilatation lasting for five beats (D1-D5). An increase in aortic diastolic pressure (32 +/- 3% for 520 +/- 15 ms) resulted in 13 +/- 2% increase in DCVRI in the D1 which was not evident in subsequent beats. Following a combined intervention, DCVRI in D1 was not significantly different from control but DCVRI did decrease to a greater degree in the subsequent response beats (D2-D7). These data indicate that the responses of two opposing vasoactive stimuli, i.e., pressure induced vasoconstriction and metabolic vasodilatation, were negated in the first response beat. The metabolically mediated vasodilatation was unaltered in the subsequent response beats.

Comparison of an automated thrombolytic predictive instrument to both diagnostic software and an expert cardiologist for diagnosis of an ST elevation acute myocardial infarction.

Because the electrocardiograms (ECGs) of patients with symptoms suggesting an acute thrombotic coronary occlusion are typically read by physicians relatively inexperienced in this skill, it is important to develop automated decision support. A Thrombolytic Predictive Instrument (TPI) is now available along with the standard diagnostic software in a commercially available electrocardiograph. This study evaluates the performance of the predictive software in comparison to both an expert cardiologist and standard diagnostic software. True sensitivity and specificity cannot be determined because acute coronary angiography was not performed. The specificities determined by this study were excellent (98% and 99%), and the sensitivities were very good (72% and 78%). These results that the TPI will be only rarely applied to patients who do not indeed have an acute coronary thrombosis. However, the reasons for even this small number of presumably falsely TPI positive patients should be determined and analyzed. It is unlikely that alterations of the thresholds for TPI activation will significantly improve on this very good level of sensitivity, without prohibitively decreasing specificity.

Coronary artery restenosis after atherectomy is primarily due to negative remodeling.

The primary cause of restenosis following directional coronary atherectomy (DCA) remains obscure. "Negative remodeling," a decrease in vessel area, is believed to be more causative than is increase in plaque area. The DCA technique used in these patients, designed to facilitate the removal of plaque, should allow a more precise evaluation of the relative roles of these two mechanisms. Twenty-five patients underwent DCA. In 17, complete angiographic and intravascular ultrasound (IVUS) images were obtained before and after DCA and at follow-up (6 to 9 months). Internal elastic lamina (IEL), lumen, and plaque areas were calculated at preatherectomy, postatherectomy, and follow-up. Postatherectomy, the mean IEL area increased by 32% and the mean plaque area decreased by 51%, resulting in a significant mean increase in lumen area, 500%. At follow-up when compared to postatherectomy, the change in IEL area was variable; however, the mean did not change significantly (p = 0.58). Plaque area change, when standardized for initial vessel size, was small (mean increase 2.8 +/- 3.5%). The mean lumen area did not decrease significantly at follow-up (p = 0.43). A highly significant correlation (r = 0.96) was noted between IEL area change and lumen area at follow-up. In contrast, the correlation between plaque area change and lumen area change over the same period was much less significant (r = 0.64). These data indicate that decrease in IEL area primarily is responsible for restenosis.

Imported African tick bite fever: a case report.

We describe a patient with African tick-bite fever who acquired his infection while visiting rural areas of South Africa and then became sick after returning to the United States. The dominant clinical feature of his illness was the presence of multiple, ulcerated lesions (tache noires). Physicians in the United States and other non-African countries who see travelers returning from southern parts of Africa who give a history of recent tick bite and/or present with multiple, crusted or vesicular skin lesions should be alert to this diagnosis and institute treatment with doxycycline.

Are interatrial band myocytes maximally hypertrophied in normal canine hearts?

In canine right atrial hypertrophy, the cross-sectional area (Axs) of right atrial myocytes increases, whereas the Axs of the broader interatrial band myocytes does not. In the current study, myocyte reconstructions showed that right atrial myocyte length increased in proportion to Axs in right atrial hypertrophy. On the other hand, mean interatrial band myocyte length in both normal and right atrial hypertrophy dogs was roughly inversely proportional to mean Axs, as expected if interatrial band myocyte volume was constant. Plotting mean Axs vs. myocyte length for individual interatrial band myocytes revealed a distribution whose border defined a maximal volume curve; many myocytes were well beneath that curve. Mononuclear myocytes (generally diploid) were limited by a 65,000-micrometer 3 curve, which many binuclear myocytes (generally tetraploid) surpassed; myocyte ploidy thus constrained myocyte volume. However, because many mononuclear and binuclear myocytes had lower volumes, their failure to hypertrophy cannot be attributed to attainment of the maximal volume possible for their ploidy.

Myocardial blood flow in awake dogs with chronic tricuspid regurgitation.

The primary purpose of this study was to define regional blood flow in dogs with chronic tricuspid regurgitation (TR) in order to determine if the marked hypertrophy of the right atria resulted in compromised myocardial perfusion. Myocardial blood flow (ml/min/gm) was measured with radiolabeled microspheres in eight dogs with TR during rest, moderate exercise (5 dogs), and infusion of adenosine (1 mg/kg/min), an index of minimal vascular resistance. Similar measurements were obtained in eight normal dogs. In TR, the ratio of right atrium (RA) and right ventricle (RV) to body weight was greater than in normal dogs, 77% and 30%, respectively. During rest, flow in the RA appendage was less than in nonappendage region in the normal dogs; no differences were noted in TR dogs, indicating an augmented hemodynamic role of the appendage in TR. Both RA and RV blood flow was greater in TR during rest but no other differences in flow were found between the two groups. Minimum vascular resistance in RV but not RA was slightly increased in TR versus normal. During marked myocyte hypertrophy, the vasculature of RA develops sufficiently to provide the same flow capacity as in the normal heart.

Myocardial oxygenation in dogs during reactive hyperemia.

The mechanisms of myocardial oxygenation during reactive hyperemia were studied in the beating heart using continuous near infrared (NIR) spectroscopy. In open chest dogs, NIR spectroscopy was used to monitor brief occlusions of the left anterior descending artery. These occlusions produced a precipitous drop in tissue oxygen stores (tHbO2+MbO2), tissue blood volume, and the oxidation level of mitochondrial cytochrome a,a3. Reperfusion produced a rapid increase in the NIR signals to supranormal levels, followed by gradual return to baseline. When the duration of occlusion was increased from 20 to 120 s, an essentially linear increase was produced in the overshoot areas defined by the NIR signals. Near infrared spectroscopy (NIRS) separated reactive hyperemia into two phases according to the tissue level of deoxyhemoglobin and deoxymyoglobin (tHb+Mb): (1) an early phase during which the tHb+Mb level was supranormal, reflecting enhanced O2 extraction; and (2) a late phase during which the tHb+Mb level was below baseline, reflecting decreased O2 extraction and increased tissue O2 availability. During reactive hyperemia, when O2 availability was maximal by NIR spectroscopy, O2 consumption was elevated but submaximal, indicating that MVO2 was not limited by O2 availability. Cytochrome a,a3 oxidation state also was restored fully. Thus, myocardial oxygenation is highly regulated during reactive hyperemia. Cellular O2 supply and mitochondrial oxidation state are restored early during reactive hyperemia by increased O2 delivery, increases in tissue blood volume and enhanced O2 extraction. © 1998 Society of Photo-Optical Instrumentation Engineers.

Regional vascular reserve in canine atria and ventricles during rest and exercise.

Vascular reserve, which defines the capacity for further vasodilation in a given physiological or pathological condition, has not been measured in the canine atria. This study defines, in normal dogs, the regional vascular reserve simultaneously measured in the atria (appendage, nonappendage regions) and in the ventricles during rest and two levels of exercise. Blood flow was determined using 11.4 +/- 0.1 microns radiolabeled microspheres. Vascular reserve (percent for each region) is the ratio of vascular conductance during each condition to maximum vascular conductance. Maximum vascular conductance was estimated by infusing adenosine intravenously. For a given physiological condition regional vascular conductance varied two- to threefold. The vascular reserve of each of the regions decreased progressively from rest to mild exercise to moderate exercise. Regional vascular reserve for both atria, the right ventricle, and the epicardial layer of the left ventricle was essentially uniform for a given condition: rest 93 +/- 0.4%, mild exercise 81 +/- 1.2%, and moderate exercise 69 +/- 1.5%. This similarity in vascular reserve implies that for a given physiological condition a common mechanism precisely regulates myocardial perfusion in these cardiac regions as a function of the total vasodilator capacity.

Regional changes in myocyte structure in model of canine right atrial hypertrophy.

To investigate regional variation of myocyte response to atrial hypertrophy, control dogs were compared with dogs with right atrial hypertrophy created by induction of tricuspid regurgitation; after 1 yr, right atrial-to-body weight ratio increased 122% over controls. One section from the interatrial band, appendage and nonappendage roofs, and nonappendage side of each atrium of each dog was stained to reveal myocyte outlines and transverse tubules; myocyte cross-sectional areas were measured and transverse tubule prevalence was estimated. In control dogs, interatrial band myocytes were significantly larger and had more transverse tubules than other atrial myocytes. With atrial hypertrophy, right interatrial band myocytes did not increase significantly in size, whereas other right atrial myocytes nearly doubled in size, approaching the size of interatrial band myocytes without approaching the content of transverse tubules. Left atrial myocytes did not increase in size. Thus hypertrophic response of atrial myocytes to hemodynamic stress depends on the region in which the myocytes are found, and atrial hypertrophy does not demand transverse tubule proliferation.

Myocardial oxygenation in dogs during partial and complete coronary artery occlusion.

Regional myocardial oxygenation was assessed during partial and complete coronary artery occlusion using near infrared spectroscopy. In eight open-chest dogs, partial occlusions resulting in an approximately 42% decrease in left anterior descending coronary artery (LAD) blood flow produced an approximately 21% decrease in tissue O2 stores (tissue oxyhemoglobin plus oxymyoglobin) and no change in the oxidation level of mitochondrial cytochrome aa3. An approximately 81% reduction in LAD blood flow produced nadir levels of tissue oxyhemoglobin plus oxymyoglobin, maximal levels of deoxyhemoglobin plus deoxymyoglobin, a decline in tissue blood volume, and an approximately 39% decrease in cytochrome aa3 oxidation level. These changes were associated with an approximately 52% decrease from the preischemic baseline in mean transmural myocardial blood flow, measured by radiolabeled microspheres, and an approximately 41% decrease in myocardial O2 consumption. Complete occlusion resulted in further decreases in myocardial blood flow, O2 consumption, tissue blood volume, and cytochrome aa3 oxidation state but also produced increases in tissue O2 stores to above the nadir levels noted during partial occlusion. These results indicate that decreases in O2 delivery during partial coronary occlusion increase O2 extraction to sustain mitochondrial O2 availability, but as little as a 52% reduction in myocardial blood flow produces maximal O2 extraction and depletion of tissue O2 stores. Mitochondrial O2 availability is restricted further during complete occlusion because of limited O2 delivery and, possibly, decreases in tissue blood volume and O2 extraction.

Regional blood flow in canine atria during exercise.

Global and regional atrial blood flow was measured with radioisotope-labeled microspheres in eight dogs during rest and two levels of exercise. Both mean right and left atrial blood flow increased significantly (P < 0.05) to a similar degree with each level of exercise (right atria: 0.27 +/- 0.04, 0.89 +/- 0.11, and 1.57 +/- 0.21 ml.min-1 x g-1; left atria: 0.35 +/- 0.04, 0.90 +/- 0.09, and 1.61 +/- 0.17 ml.min-1 x g-1). Atrial blood flow during exercise is greater than anticipated if increased heart rate was the sole cause. In both right and left atria the ratio of appendage to nonappendage flow was significantly (P < 0.005) less than one during resting conditions (0.42 +/- 0.04 and 0.81 +/- 0.05, respectively), not different from unity during mild exercise, and significantly (P < 0.02) greater than one during moderate exercise (1.10 +/- 0.03 and 1.16 +/- 0.05, respectively). This disparity in the blood flow to the appendage and nonappendage regions suggests that the appendage plays an augmented hemodynamic role during exercise, thus requiring a larger proportion of the nutrient flow.

Distinction between metabolic and myogenic mechanisms of coronary hyperemic response to brief diastolic occlusion.

We monitored an index of coronary vascular resistance (mean aortic pressure/mean coronary flow) in 19 heart-blocked conscious dogs paced at 60 beats/min and instrumented with an aortic pressure catheter, left circumflex artery electromagnetic flow probe, and a coronary occluder. Cessation of pacing for a single beat resulted in a long diastole control (LDC) intervention beat of 2-second duration characterized by a progressive rise in diastolic coronary vascular resistance index. A 400-msec coronary artery occlusion early in a long diastole (LD4) dramatically inhibited the rate of rise in resistance index during the first 600 msec (phase 1) after occlusion. Partial recovery of the resistance index rise rate was evident during the remaining 400 msec (phase 2) of the long diastole. In nine dogs, LDC and LD4 intervention beats were instituted during two conditions of myocardial metabolic activity in which the myogenic stimuli associated with coronary occlusion would be similar: 1) paired pacing and 2) normal pacing plus intravenous adenosine and phenylephrine infusions (AP) to maintain mean aortic pressure and coronary flow at paired pacing levels. During paired pacing, the LD4-LDC differences in phase 1 and 2 resistance index rise rates (-69 +/- 18 and -48 +/- 31 mmHg/ml/sec2, respectively) were greater than during normal pacing plus AP (-32 +/- 14 and -1 +/- 32 mm Hg/ml/sec2, phase 1 and 2, respectively) (p less than 0.05). These differences are consistent with operation of a metabolic mechanism in response to occlusion.(ABSTRACT TRUNCATED AT 250 WORDS)

In vitro evaluation of the plasma and blood compatibility of a parenteral formulation for ditekiren, a novel renin inhibitor pseudopeptide.

Ditekiren (U-71038; Boc-Pro-Phe-N-MeHis-Leu-psi[CHOHCH2]-Val-Ile-(aminomethyl)pyridine ) is a potent renin inhibitor peptide and was formulated for clinical intravenous administration in acidified dextrose. This formulation of ditekiren was evaluated in vitro with human and monkey plasma as to its potential for forming a precipitate either of drug or of plasma proteins. Analysis by centrifugation showed that no drug precipitation occurred in plasma from either species at concentrations 25 times higher than anticipated in clinical studies. Results obtained by turbidimetry indicated that formulated ditekiren did not cause aggregation of human platelets or flocculation of proteins at concentrations approaching the solubility limit of the drug in plasma. Ditekiren or vehicle also caused no detectable lysis of red cells at concentrations representing 10 times the maximum clinical level. Therefore, ditekiren solutions as formulated are judged completely compatible with blood and plasma upon clinical intravenous administration.

Hemodynamic and myocardial blood flow. Profiles of pinacidil and nitroprusside in conscious dogs.

Vasodilator antihypertensive agents can induce endocardial underperfusion relative to myocardial metabolic demand in normal hearts. We studied ten conscious normotensive dogs, paced at constant heart rate, to determine the relative probabilities of inducing endocardial ischemia with intravenous sodium nitroprusside or pinacidil, a novel antihypertensive agent. On different days, pinacidil and nitroprusside were infused in each animal to achieve mean aortic pressures (MAP) of 83 +/- 0.2 mm Hg and 62 +/- 1 mm Hg, reduced from control pressures of 106 +/- 3 mm Hg (pinacidil) and 107 +/- 3 mm Hg (nitroprusside). At MAP = 62 mm Hg, pinacidil depressed the left ventricular endocardial:epicardial blood flow (0.81 +/- 0.03) more than did nitroprusside (1.00 +/- 0.06, P less than .01). However, pinacidil increased left ventricular blood flow in all transmural layers at both levels of hypotension (P less than .05); nitroprusside increased only epicardial blood flow at MAP = 62 mm Hg (P less than .05). Neither vasodilator significantly altered myocardial oxygen consumption at either level of hypotension. At MAP = 83 mm Hg, pinacidil depressed the ratio of left ventricular vascular resistance and systemic vascular resistance indices (LVVRI/SVRI) 40 +/- 6 percent (P less than .001) to a level below that existing during nitroprusside infusion (P less than .05). These data indicate that pinacidil has greater selectivity for the coronary circulation over the systemic circulation compared to nitroprusside. Although it is unlikely that either drug caused endocardial ischemia in the present study, the data suggest that pinacidil is less likely to do so than is nitroprusside in normal hearts.

Dynamic mechanisms of cardiac oxygenation during brief ischemia and reperfusion.

Myocardial oxygenation may be altered markedly by changes in tissue blood flow. During brief ischemia and reperfusion produced by transient occlusion of the left anterior descending artery in 10 open-chest dogs, changes in the oxygenation of tissue hemoglobin (Hb) plus myoglobin (Mb) and the oxidation-reduction (redox) state of mitochondrial cytochrome aa3 were monitored continuously using near-infrared spectroscopy. The nondestructive optical technique indicated that coronary occlusion produced an abrupt drop in tissue oxygen stores (tHb02 + Mb02), tissue blood volume (tBV), and the oxidation level of cytochrome aa3. Changes in the cytochrome oxidation state were related inversely to transmural collateral blood flow within the ischemic region (r = 0.77) measured with radiolabeled microspheres. Furthermore, there was a direct relationship (r = 0.91) between collateral blood flow and the tissue level of desaturated Hb and Mb (tHb + Mb). Reperfusion after 2 min of ischemia led to a synchronous overshoot of baseline in coronary flow and tBV followed by supranormal increases in tHb + Mb02 and the oxidation level of cytochrome aa3. The tHb + Mb level increased transiently during reperfusion. This response correlated inversely with collateral flow during ischemia (r = 0.91). Accordingly, the time required to reach peak tHb + Mb levels was shortest in dogs with high collateral flows (r = 0.75). Thus collateral blood flow partially sustains myocardial oxygenation during coronary artery occlusion and influences tissue reoxygenation early during reperfusion.