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Biomedical subjects

J D Bergin

Publications and source records attributed to J D Bergin.

At least 19 recordsLinked to original sources

Acute cardiovascular effects of OPC-18790 in patients with congestive heart failure. Time- and dose-dependence analysis based on pressure-volume relations.

BACKGROUND: OPC-18790 is a water-soluble quinolinone derivative that shares the pharmacological properties of vesnarinone and that may be useful for treating heart failure. We studied the contribution and relative dose sensitivities of the inotropic, lusitropic, and vascular effects of OPC-18790 in patients with dilated cardiomyopathy. METHODS AND RESULTS: Pressure-volume (PV) analysis was performed in 17 patients who received either 5 micrograms.kg-1.min-1 (low dose, n = 10) or 10 micrograms.kg-1.min-1 (high dose, n = 7) OPC-18790 by 1-hour IV infusion. Right heart pressures and flow and left heart PV relations (conductance catheter) were measured at baseline and every 15 minutes during infusion. Transient inferior vena caval obstruction was used to determine PV relations. Both doses produced venodilation reflected by a 10% decline in left ventricular end-diastolic volume and a 30% fall in atrial and pulmonary artery pressures. Arterial dilation was four times greater at the high dose, with an approximately 40% fall in effective arterial elastance and systemic resistance. Contractility rose by 25% to 100% (depending on PV index) with both doses. Ventricular-arterial coupling (ratio of ventricular end-systolic to arterial elastances) was approximately 0.25 at baseline and doubled (or tripled) at low (or high) dose, correlating with improved efficiency. Isovolumetric relaxation shortened, whereas the diastolic PV relation was generally unchanged. Heart rate was unaltered. CONCLUSIONS: OPC-18790 has potent venous and arterial vasodilator effects and moderate inotropic and lusitropic effects without a change in heart rate. These combined actions suggest a unique potential of OPC-18790 for heart failure treatment.

Blood Pressure↗

Cardiac transplantation for the cardiologist not trained in transplantation.

This review focuses on selected aspects of the treatment of patients being evaluated for and undergoing cardiac transplantation. Cardiac transplantation is a potential therapeutic option for a variety of irreversible cardiac disorders when the symptomatic status and anticipated survival after transplantation exceeds that of the patient's condition. The timing of cardiac transplantation with respect to prognosis is aided by the measurement of baseline hemodynamics and maximal aerobic capacity. Major cardiac problems that occur after transplantation include an increased early risk of acute allograft rejection and, later, the occurrence of allograft coronary artery disease. Furthermore, cardiac transplant recipients have unique "normal" physiologic alterations with respect to intracardiac hemodynamics, exercise capacity, the effects of denervation, and expected electrocardiographic and echocardiographic findings.

Heart Failure↗

General surgical complications can be predicted after cardiopulmonary bypass.

OBJECTIVE: The authors review the general surgical complications of cardiopulmonary bypass, including newer procedures such as heart and lung transplantation, to identify patients at higher risk. SUMMARY BACKGROUND DATA: Although rare, the general surgical complications of cardiopulmonary bypass are associated with high mortality. The early identification of patients at increased risk for these complications may allow for earlier detection and treatment of these problems to reduce mortality. METHODS: A retrospective review was performed of 1831 patients undergoing cardiopulmonary bypass from 1991 to 1993. This was done to identify factors that significantly contributed to an increased risk of general surgical complications. RESULTS: Factors associated with an increased risk of general surgical complications included prolonged cardiopulmonary bypass (p < 0.005) and intensive care unit stay (p < 0.002), occurrence of arrhythmias (p < 0.001), use of inotropic agents (preoperatively or postoperatively p < 0.001), insertion of the intra-aortic balloon pump (preoperatively p < 0.005, postoperatively p < 0.001), use of steroids (p < 0.001), and prolonged ventilator support (p < 0.001). Multivariate analysis identified use of the intra-aortic balloon pump (p < 0.001) as the strongest predictor of the general surgical complications of cardiopulmonary bypass. A variety of factors not contributing significantly to an increased risk also were identified. CONCLUSIONS: Factors indicative of or contributing to periods of decreased end-organ perfusion appear to be significantly related to general surgical complications after cardiopulmonary bypass.

Aged↗

Successful use of undersized donors for orthotopic heart transplantation--with a caveat.

Accepted clinical practice has been to require body weights to be within 20% as a criterion for matching donor to recipient for cardiac transplantation. From November 1989 through September 1993 we began accepting larger differences in body weight between donor and recipient with 80 orthotopic heart transplants performed. Twenty-eight of these transplants used undersized donors (donor-to-recipient body weight ratio [DRBW] of 0.6 to 0.8) with the remaining donors being either size matched (DRBW = 0.8 to 1.0) or oversized (DRBW > 1.0). Thirty-three of the 80 transplant recipients (41%) were classified preoperatively as United Network for Organ Sharing (UNOS) status I and the remaining patients were classified as UNOS status II. Hospital survival for status I recipients was 9 of 14 (64%) for undersized donors, 7 of 8 (87.5%) for sized-matched donors, and 11 of 11 (100%) for oversized donors (p < 0.05). Hospital survival for status II recipients was 12 of 14 (85.7%) for undersized donors, 24 of 24 (100%) for sized-matched donors, and 8 of 9 (88.8%) for oversized donors. Our data support the continued use of hearts from undersized donors in status II recipients. The use of hearts from undersized donors in status I recipients is associated with increased mortality compared with size-matched donors and must be undertaken with caution.

Adult↗

Ambulatory intraaortic balloon counterpulsation.

A technique is described for the retroperitoneal placement of a balloon pump that preserves patient mobility. This technique may be superior to standard femoral placement when prolonged support is required for cardiac transplant candidates awaiting donor organs.

Ambulatory Care↗

Redistribution of 99mTc-sestamibi and 201Tl in the presence of a severe coronary artery stenosis.

BACKGROUND: 99mTc-labeled methoxyisobutyl isonitrile (99mTc-sestamibi) is a myocardial perfusion agent that clears slowly from the myocardium. This study evaluates the early and late myocardial distributions of 99mTc-sestamibi and 201Tl in the presence of low-flow ischemia to determine whether 99mTc-sestamibi demonstrates rest "redistribution." METHODS AND RESULTS: Low-flow ischemia was produced in 18 anesthetized, open-chest dogs by partial occlusion of the left anterior descending coronary artery. Dogs were injected intravenously with 99mTc-sestamibi, 301Tl, and radiolabeled microspheres during sustained low-flow ischemia. The hearts were excised either 20 minutes (group 1, 10 dogs) or 2.5 hours (group 2, 8 dogs) after injection for gamma well counting to evaluate the early and late myocardial distributions of these radiotracers, relative to microsphere flow. The early myocardial distributions of 99mTc-sestamibi and 201Tl were comparable and correlated with the flow deficit (group 1). We observed a significant difference in myocardial 201Tl (P = .005) and 99mTc-sestamibi (P < .0001) activities between groups 1 and 2 dogs relative to flow, suggesting some redistribution of both tracers. Myocardial slices were imaged postmortem with a gamma camera, and 99mTc-sestamibi defect intensity was quantified. There was excellent correlation (r = .97) between the early relative 99mTc-sestamibi defect intensity on postmortem images and the flow deficit (group 1). Among group 2 dogs, the correlation was good (r = .87), but the 99mTc-sestamibi defect was less severe than the flow deficit, again suggesting redistribution. CONCLUSIONS: The myocardial distributions of 99mTc-sestamibi and 201Tl early after injection are comparable and proportional to flow. Under conditions of sustained low flow, there was detectable rest "redistribution" of 99mTc-sestamibi verified by both gamma well counting and high-resolution postmortem imaging of myocardial slices. Whether this degree of 99mTc-sestamibi rest redistribution will be detectable by serial clinical imaging remains uncertain. Nevertheless, these data suggest that imaging should be delayed after the resting injection of 99mTc-sestamibi when assessing myocardial viability in the presence of a critical stenosis.

Animals↗

Noninvasive assessment of systolic and diastolic function. Important clues to differentiating types of congestive heart failure.

The clinical distinction between systolic and diastolic dysfunction as the cause for congestive heart failure (CHF) is readily made with noninvasive diagnostic testing. Patient history, physical examination, chest films, and electrocardiography provide readily obtainable clues to the presence of left ventricular dysfunction. Noninvasive imaging methods are an important quantitative adjunct in evaluation. Among these, echocardiography and radionuclide angiography are the most widely available and accepted techniques. Other advances, such as new radionuclide imaging agents, cine magnetic resonance imaging, and cine computed tomographic scanning, may also be useful in selected circumstances. Functional assessments using ventilatory gas analysis can aid in the evaluation of patients with CHF and in the timing of intervention with cardiac transplantation.

Diastole↗

Bolus intravenous nitroglycerin predominantly reduces afterload in patients with excessive arterial elastance.

OBJECTIVES: We hypothesized that bolus intravenous nitroglycerin would be an afterload-reducing agent in patients with excessive initial afterload for their level of left ventricular systolic function. Conversely, bolus intravenous nitroglycerin should be a preload-reducing agent in patients without excessive initial afterload. BACKGROUND: Although nitroglycerin has both preload- and afterload-reducing actions, methods to predict its predominant site of action in an individual patient have not been previously described. METHODS: Left ventricular pressure-volume relations were recorded with micromanometer and conductance catheters during bolus injection of intravenous nitroglycerin in 27 patients with both normal left ventricular systolic function and varying degrees of congestive heart failure. Preload was determined by end-diastolic volume, afterload by effective arterial elastance, left ventricular systolic function by end-systolic elastance and coupling of afterload and ventricular function by the ratio of effective arterial elastance to end-systolic elastance (Ea/Ees ratio). An Ea/Ees ratio > 1 was defined as excessive afterload for the level of ventricular function. RESULTS: Patients with an initial Ea/Ees ratio < 1 (Group 1) constituted a group of normotensive patients with intact ventricular function who exhibited a predominant reduction in preload in response to intravenous nitroglycerin. Those with an initial Ea/Ees ratio > 1 and normal or mildly depressed ventricular function (Group 2a) constituted a group of patients, most of whom were hypertensive, who exhibited a predominant afterload reduction. Finally, those with an initial Ea/Ees ratio > 1 and abnormal ventricular function (Group 2b) constituted a group of patients with clinical congestive heart failure who exhibited both preload and afterload reduction but a predominant afterload reduction because stroke volume increased. CONCLUSIONS: Patients with normal arterial elastance and ventricular function respond to nitroglycerin with a predominant preload reduction, whereas patients with either excessive arterial elastance or abnormal ventricular function respond with a predominant afterload reduction.

Analysis of Variance↗

Successful transplantation of marginally acceptable thoracic organs.

OBJECTIVE: This study evaluates the efficacy of personally inspecting marginal thoracic organ donors to expand the donor pool. SUMMARY BACKGROUND DATA: The present donor criteria for heart and lung transplantation are very strict and result in exclusion of many potential thoracic organ donors. Due to a limited donor pool, 20-30% of patients die waiting for transplantation. METHODS: The authors have performed a prospective study of personally inspecting marginal donor organs that previously would have been rejected by standard donor criteria. RESULTS: Fourteen marginal hearts and eleven marginal lungs were inspected. All 14 marginal hearts and 10 of the marginal lungs were transplanted. All cardiac transplant patients did well. The mean ejection fraction of the donor hearts preoperatively was 39 +/- 11% (range 15-50%). Postoperatively, the ejection fraction of the donor hearts improved significantly to 55 +/- 3% (p < 0.002). Nine of the ten lung transplant patients did well and were operative survivors. Our donor pool expanded by 36% over the study period. CONCLUSIONS: The present donor criteria for heart and lung transplantation are too strict. Personal inspection of marginal thoracic donor organs will help to maximize donor utilization.

Heart↗

Why do patients with congestive heart failure tolerate the initiation of beta-blocker therapy?

BACKGROUND: Despite its negative inotropic effects, the initiation of beta-adrenergic blockade is tolerated by patients with congestive heart failure (CHF). Accordingly, we examined the acute hemodynamic effects of beta-adrenergic blockade on systolic and diastolic left ventricular (LV) function and ventriculo-arterial coupling. In addition, isolated myocardium from patients with CHF shows selective beta 1-receptor downregulation, implying a greater role for the beta 2-receptor in maintaining in vivo LV contractility. As a secondary aim, we hypothesized that nonselective beta-adrenergic blockade would have greater negative inotropic effect than beta 1-blockade in patients with CHF. METHODS AND RESULTS: Patients with clinical CHF (n = 24) and control patients without CHF (n = 24) were given either the nonselective beta-blocker propranolol or the beta 1-selective blocker metoprolol. LV pressure-volume relations were obtained before and after the administration of intravenous beta-blocker, and measures of LV systolic and diastolic function were examined. Patients with CHF had a deterioration in LV systolic function with a fall in LV systolic pressure (139 +/- 6 to 125 +/- 6 mm Hg), cardiac index (2.56 +/- 0.11 to 2.20 +/- 0.11 mL.min-1 x M-1), dP/dtmax (1173 +/- 63 to 897 +/- 50 mm Hg/s), and end-systolic elastance (0.88 +/- 0.10 to 0.64 +/- 0.10 mm Hg/mL), P < .05 for all. Although there was deterioration of active LV relaxation (isovolumetric relaxation 63 +/- 2 to 73 +/- 3 milliseconds, peak filling rate 543 +/- 33 to 464 +/- 28 mL/s, P < .05 for both), there was no change in passive LV diastolic function (pulmonary capillary wedge, 24 +/- 2 to 24 +/- 1 mm Hg; chamber stiffness, 0.0154 +/- 0.0005 to 0.0163 +/- 0.0005 mL-1, P = NS for both), and a decrease in afterload (arterial elastance 3.85 +/- 0.31 to 3.38 +/- 0.24 mm Hg/mL, P < .05). Control patients had no change in these parameters other than a prolongation of isovolumetric relaxation (48 +/- 1 to 55 +/- 2 milliseconds, P < .05). The effects of propranolol (n = 12) versus metoprolol (n = 12) on these parameters in patients with CHF were similar. CONCLUSIONS: These data do not support a greater in vivo physiological role of the myocardial beta 2-receptor in CHF. The preservation of passive diastolic function and ventriculo-arterial coupling provide possible explanations of why beta-adrenergic blockade is tolerated by patients with CHF.

Adrenergic beta-Antagonists↗

Influence of subendocardial ischemia on transmural myocardial function.

The relationship between regional myocardial perfusion and function under ischemic conditions was examined by using a nontraumatic single-crystal pulsed Doppler system that permits complete transmural assessment of myocardial thickening. Sixteen open-chest dogs underwent either 50 (n = 4) or 180 (n = 12) min of partial coronary artery occlusion. Simultaneous measurements of myocardial thickening fraction (TF) and microsphere-determined blood flow (BF) were taken in the subepicardial, midwall, and subendocardial thirds of the left ventricular wall. During ischemia, there was an excellent correlation between BF and TF in the subendocardium. Mean subendocardial BF was reduced to 0.45 +/- 0.3 ml.min-1.g-1, resulting in a subendocardial TF of 0.8 +/- 19%. Although subepicardial BF was relatively preserved at 1.03 +/- 0.4 ml.min-1.g-1, subepicardial TF was diminished markedly and not significantly different from subendocardial TF. Subepicardial and midwall TF were highly dependent on subendocardial flow rather than on the actual flow in these areas. Hence these studies show a marked dependence of transmural myocardial function on subendocardial blood flow. Outer wall function is more dependent on subendocardial than subepicardial blood flow.

Animals↗

Weight is not an accurate criterion for adult cardiac transplant size matching.

Owing to the limited availability of donor hearts, standard donor criteria for heart size matching need to be reexamined. The current practice at most centers is to match the donor's body weight to within +/- 20% of the recipient's. Our hypothesis was that minimal differences exist in heart sizes of the adult donor population, and therefore, the donor pool could be expanded for any given patient. M-mode echocardiographic measurements of left and right ventricular internal dimensions, left ventricular mass, and percent fractional shortening were reviewed in 235 normal adult subjects (101 men, 134 women). Low correlation coefficients and a high degree of variance were consistently observed between cardiac parameters and body size. There were no significant differences in left ventricular internal dimension when women weighing 40 to 109 kg were compared with men statistically different among men weighing 50 to 99 kg. No difference was noted in right ventricular size among men and women. Echocardiography is a simple and accurate technique to assess cardiac dimensions. Body weight does not correlate well with adult cardiac size and should not be used as an exclusion criterion for a donor heart.

Body Height↗

Quantification of area at risk during coronary occlusion and degree of myocardial salvage after reperfusion with technetium-99m methoxyisobutyl isonitrile.

Serial myocardial imaging with technetium-99m methoxyisobutyl isonitrile (99mTc-MIBI) has been proposed for evaluating myocardial salvage after reperfusion. To define 99mTc-MIBI uptake before and after reperfusion, 17 open-chest dogs underwent 3 hours of left anterior descending artery occlusion and 3 hours of reperfusion. 99mTc-MIBI was injected during occlusion (group 1) or after 90 minutes of reperfusion (group 2). Myocardial 99mTc-MIBI activity was correlated with microsphere flow during occlusion and reperfusion. Anatomic risk area and infarct area were defined by postmortem vital staining and correlated with the perfusion defects defined by analysis of 99mTc-MIBI macroautoradiographs and gamma camera images of myocardial slices. The left ventricle was divided into 96 segments for gamma well counting. Flow and 99mTc-MIBI activity were normalized to nonischemic values. Myocardial segments were grouped, based on occlusion flow, into zones: severely ischemic (less than or equal to 30% nonischemic), moderately ischemic (greater than 30%, less than or equal to 60% nonischemic), mildly ischemic (greater than 60%, less than or equal to 90% nonischemic), and nonischemic (greater than 90%, less than or equal to 120% nonischemic). Among dogs injected with 99mTc-MIBI during coronary occlusion (group 1), myocardial 99mTc-MIBI activity correlated linearly with occlusion flow for both endocardial (r = 0.91) and transmural (r = 0.91) segments. The risk area defined by 99mTc-MIBI autoradiography (group 1) correlated with the postmortem risk area (rho = 0.94) but was 29% smaller than the anatomic risk area (p = 0.03), reflecting the contribution of collateral flow. Among dogs injected with 99mTc-MIBI after reperfusion (group 2), myocardial 99mTc-MIBI did not correlate with reperfusion flow in either endocardial or transmural segments. Among group 2 dogs, myocardial 99mTc-MIBI activity was significantly less than reperfusion flow at the time of injection in the severely ischemic (25 +/- 5% versus 74 +/- 24% nonischemic, p = 0.002), moderately ischemic (54 +/- 12% versus 96 +/- 15% nonischemic, p = 0.001), and mildly ischemic (84 +/- 6% versus 93 +/- 3% nonischemic, p = 0.002) zones. The defect area defined by 99mTc-MIBI autoradiography (group 2) correlated very closely with the postmortem infarct area (rho = 0.98). Thus, the myocardial uptake of 99mTc-MIBI during coronary occlusion correlates with occlusion flow and reflects the "area at risk." When 99mTc-MIBI was given after 90 minutes of reperfusion following 3 hours of coronary occlusion, the myocardial activity was significantly reduced compared with reperfusion flow in both necrotic and perinecrotic regions, reflecting myocardial viability more than the degree of reperfusion.

Animals↗

Inhibition of aminopeptidase M by alkyl D-cysteinates.

Ethyl D-cysteinate is a potent competitive inhibitor (Ki = 3.5 x 10(-7) M) of aminopeptidase M. D-cysteine and ethyl L-cysteinate inhibit more than two orders of magnitude less effectively. Inhibition studies on several n-alkyl esters of D-cysteine reveal an optimum at the n-butyl ester (Ki = 1.8 x 10(-7) M). The results are consistent with the hypothesis that the thiol group coordinates to Zn+2 at the active site and the alkyl group occupies the hydrophobic binding site for the side chain of the amino-terminal residue of substrates. Cytosolic leucine aminopeptidase is not significantly inhibited by ethyl D-cysteinate.

Aminopeptidases↗