Evaluation of hemodynamic parameters in patients with right ventricular infarction during rehabilitation

Hemodynamic data in 43 patients with right and left ventricular infarction and 39 with left ventricular infarction were compared. Right atrial pressure, pulmonary capillary wedge pressure, mean pulmonary artery pressure, left ventricular end-diastolic pressure before and after ventricular angiogram, cardiac index, left ventricular stroke volume index, right ventricular stroke work index were evaluated, as well as ratios of right atrial and pulmonary capillary wedge pressure, right and left ventricular end-diastolic pressure, right ventricular end-diastolic and pulmonary capillary wedge pressure, left ventricular ejection fraction calculated from left ventricular angiogram, Berentey's score, and cardiac volume index. Using ONEWAY analysis there was no significant difference between the two groups in period of rehabilitation. In 15 patients with right ventricular infarction regression of ECG changes was observed in lead V3R also without significant influence on hemodynamic data.     

Comparison of left and right ventricular function in acute myocardial infarction

Pulmonary arterial end-diastolic and mean right atrial pressures were compared in 25 patients with acute myocardial infarction and in one patient with unstable angina. No consistent relationship was observed between these pressures. Simultaneous ventricular function curves relating the stroke work of each ventricle to its respective filling pressure were constructed on 34 occasions, dextran infusion or diuresis being used to alter the filling pressure. The curves from each ventricle were described mathematically by a quadratic (parabolic) function as well as by a straight line function and then compared by canonical correlation analysis. Alterations in the left ventricular function curves occurred with and without depression or right ventricular function curves. These hemodynamic measurements demonstrate that acute myocardial infarction can alter the relationship between left and right ventricular function.     

Clinical implications of left ventricular function in patients with acute myocardial infarction

Correlation of left ventricular filling pressure (55 patients) with the left ventricular stroke work index (61 patients) provided a rapid means of objectively determining ventricular performance after myocardial infarction. Pressure was monitored by means of the Swan-Ganz balloon-tipped catheter and thermal indicators were used for measuring cardiac output. A hemodynamic grouping of these myocardial infarction patients on the basis of the stroke work index showed close correlation with morbidity and mortality and provided a more accurate prognostic indicator than did the commonly used clinical predictors. Serial assessment of ventricular function further aided in defining the prognosis when it was not clear on admission. Thus, the levels of normal or abnormal ventricular function and the effect of therapeutic measures can be rapidly evaluated by determining the pressures and flows in patients with acute myocardial infarction.     

New aspects of the treatment of left ventricular failure: Nitroglycerin (author's transl)

The effectiveness of Nitroglycerin and its derivates in angina pectoris is well-known. One of the main effects is the reduction of left ventricular filling pressure. Therefore in patients with left ventricular failure after acute myocardial infarction or with chronic coronary heart disease the indication for Nitroglycerin has to be proved. In 51 patients with 76 measurements Nitroglycerin sublingual, intravenous Nitroglycerin, Isosorbide-Dinitrate and Myocardon were investigated. All substances decreased pulmonary artery pressure especially left ventricular filling pressure. Cardiac output increased or decreased in dependence to the height of left ventricular enddiastolic pressure. In the patients with myocardial infarction and left ventricular failure with filling pressures over 20 mm Hg a significant increase in cardiac output was observed. On the contrary in patients without left ventricular failure cardiac output decreased slightly. Nitroglycerin sublingual is especially useful in the most severe form of left ventricular failure: in pulmonary oedema. 0.8 mg of Nitroglycerin 3 to 4 times in 5 to 10 minutes distance is necessary dependent on the severity of the pulmonary oedema and the height of the blood pressure. The permanent intravenous infusion of Nitroglycerin (3 to 6 mg per hour) is very efficient in the treatment of congestive failure in acute myocardial infarction. The left ventricular filling pressure decreased from 28 to 16 mm Hg with an increase in cardiac output from 3.5 to 4.01/min. The mean arterial pressure dropped about 10 mm Hg. Also with oral derivates of Nitroglycerin (Isosorbide-Dinitrate and Myocardon) an extensive decrease in left ventricular filling pressure and an increase in cardiac output has been observed in patients with left heart failure.     

Left ventricular hemodynamics and function in acute myocardial infarction: studies during the acute phase, convalescence and late recovery

The left ventricular hemodynamics of 70 patients with acute myocardial infarction were determined from measurements of pulmonary arterial end-diastolic pressure, cardiac index, mean arterial pressure and heart rate during the acute phase(first study, 5 hours after admission), 4 to 6 weeks later (second study, during convalescence) and in 35 percent of all subjects 6 to 12 months after the acute infarction (third study). Serial analysis of serum creatine kinase was carried out during the acute phase. The peak CK value normalized for body surface area was used as a rough index of the extent of the acute myocardial necrosis. The condition of all survivors of the acute stage improved. Patients with only slightly reduced left ventricular performance during the acute stage recovered to nearly normal during convalescence. The condition of patients with greatly reduced left ventricular function also improved but remained impaired during convalescence. In all patients the main changes in left ventricular hemodynamics occurred within the first 4 to 6 weeks; there was almost no further alteration during the following 9 months.     

Effect of hypertonic saline solution and dextran on ventricular blood flow and heart-lung interaction after hemorrhagic shock

BACKGROUND: Hypertonic saline solutions may have beneficial hemodynamic effects in the resuscitation of hemorrhagic shock. The effects on cardiac function and potential interaction with lung function are controversial and served as the basis for this study. METHODS: Domestic swine were resuscitated from hemorrhagic shock with equivalent sodium loads of lactated Ringer's solution (LR) or 7.5% NaCl plus 10% dextran (HSD). Hemodynamic data were obtained at baseline, shock, and after resuscitation. Right ventricular ejection fraction and left ventricular change in pressure with respect to time (dP/dt) were used to index contractility. Regional myocardial blood flow was determined with microspheres. Lung water was determined gravimetrically. RESULTS: There were no differences in the ability to restore hemodynamic parameters with equivalent sodium loads of LR and HSD resuscitation. Right ventricular ejection fraction and left ventricular change in pressure with respect to time were only transiently affected by shock and resuscitation. Regional myocardial blood flow was increased above baseline values after HSD. The total resuscitation volumes were 1958 +/- 750 mL and 140 +/- 31 mL with LR and HSD, respectively. CONCLUSIONS: Although LR and HSD were equally effective in the early resuscitation of hemorrhagic shock, this occurred at the expense of significantly greater volume requirements for resuscitation with LR. This may contribute to cardiac dysfunction in this setting. Enhanced regional myocardial blood flow after HSD resuscitation may be beneficial against ongoing myocardial stress.     

Experimental rat model representing both acute and chronic heart failure related to autoimmune myocarditis

The most important clinical manifestation of myocarditis is congestive heart failure. The precise mechanisms of heart failure during myocarditis have not been elucidated because no animal model that would permit in vivo study of hemodynamics in severe active myocarditis has been available. We monitored hemodynamics and left ventricular function in a rat model of experimental autoimmune myocarditis to determine if this model could be useful for the study of in vivo hemodynamics in severe active myocarditis. Lewis rats were immunized with human cardiac myosin suspended in complete Freund's adjuvant. Baseline hemodynamics were measured using an ultraminiature catheter pressure transducer via the right internal carotid artery, 4 weeks after immunization in one group of rats (acute phase) and 3 months after immunization in another group (chronic phase). Untreated rats served as the control group. Hemodynamic measurements were also obtained after infusion of dobutamine in the acute-phase and chronic-phase groups. The heart weight-to-body weight ratios were significantly higher in both the acute-phase group and the chronic-phase group compared with normal control rats. The baseline left ventricular systolic pressure was significantly lower in the chronic phase group than in the control group. Peak dP/dt and peak -dP/dt were significantly lower in both the acute-phase group and the chronic-phase group compared with the control group. Dobutamine significantly increased left ventricular systolic pressure, peak dP/dt, and peak -dP/dt in the chronic-phase group but caused only minor changes in hemodynamic variables in the acute-phase group. In vivo measurements of hemodynamic variables indicated the presence of left ventricular dysfunction in rats with experimental autoimmune myocarditis. This animal model may be useful for the study of both acute heart failure related to acute myocarditis and chronic heart failure due to diffuse myocardial fibrosis.     

Transmyocardial laser revascularization fails to prevent left ventricular functional deterioration and aneurysm formation after acute myocardial infarction in sheep

OBJECTIVE: Transmyocardial laser revascularization is an investigational technique for revascularizing ischemic myocardium in patients with inoperable coronary arterial disease. This study tests the hypothesis that laser revascularization prevents left ventricular functional deterioration and aneurysm formation after acute anteroapical myocardial infarction. METHODS: An ultrasonic ascending aortic flow probe and snares around the distal left anterior descending and second diagonal coronary arteries were placed in 26 Dorsett hybrid sheep. Ten to 14 days later, snared arteries were occluded to produce an anteroapical infarction of 23% of left ventricular mass. Before infarction 14 animals had 34 +/- 4 transmyocardial perforations in the area of the anticipated infarction made with a carbon dioxide laser. Twelve animals served as controls. Hemodynamic measurements and transdiaphragmatic quantitative echocardiograms were obtained before, immediately after, and 2, 5, and 8 weeks after infarction. Eighteen sheep completed the protocol. RESULTS: All animals had large anteroapical left ventricular aneurysms with massive ventricular enlargement. Immediately after infarction the anterior wall became thinner and dyskinetic in all sheep. At 8 weeks aneurysmal size and shape were indistinguishable between groups. Two days after infarction, laser holes were filled with fibrin. At 5 and 8 weeks the infarct consisted of dense collagen, fibroblasts, scattered calcifications, myocyte fragments, neutrophils, macrophages, and no laser holes. There were no significant differences at any time between groups for cardiac pressures or output, ventricular volumes, ejection fraction, stroke work, and the stroke work-left ventricular end-diastolic pressure index. CONCLUSION: Transmyocardial laser perforations do not revascularize acute myocardial infarction in sheep.     

High stroke volume para-aortic counterpulsation device versus centrifugal pump in cardiogenic shock: experimental study

During the last decades a number of left ventricular assist devices has been used especially for patients resistant to pharmacologic treatment and to intraaortic balloon pump (IABP) support for left ventricular failure. A high stroke volume para-aortic counterpulsation device (PACD) has been developed utilizing the principle of the diastolic counterpulsation technique. In this study the hemodynamic effects of the valveless PACD were compared to those of the centrifugal blood pump (CBP) in nine dogs in acute experimental cardiogenic shock. Hemodynamic measurements were obtained at baseline with both devices off, PACD on and CBP off, or PACD off and CBP on. There was no difference in mean aortic pressure between PACD on (60.0 +/- 11.5 mmHg) and CBP on (69.0 +/- 26.8 mmHg). Similarly, there was no difference in left ventricular end-diastolic pressure with the PACD on (11.9 +/- 5.4 mmHg) versus the CBP on (9.9 +/- 5.2 mmHg) or the cardiac index with the PACD on (84 +/- 36 ml/kg/min) versus the CBP on (77 +/- 36 ml/kg/min). However, the left ventricular systolic pressure (55.0 +/- 19.0 with PACD versus 73.0 +/- 26.0 with CBP,p < 0.001), the tension time index (712 +/- 381 versus 1333 +/- 694,p < 0.01), and the double product (5629 +/- 2574 versus 7440 +/- 3294,p < 0.01) were significantly lower during assistance with the PACD than with the CBP. It was concluded that PACD is at least as effective as CBP for restoring hemodynamic status during acute experimental cardiogenic shock. Moreover, the PACD unloads the left ventricle more effectively than CBP, making it suitable for left ventricular mechanical support in cases with reversible myocardial damage.     

Early and late postinfarct dilatation of the left ventricle: the connection to electrophysiological disorders and the risk of developing ventricular tachyarrhythmias

The aim of the study was to discover determinants of the onset of life threatening ventricular tachyarrhythmia. 102 patients with acute myocardial infarction and 32 patients with postinfarction cardiosclerosis were examined. The data gained at programmed ventricular stimulation, high resolution ECG, Holter ECG monitoring, spectral analysis of cardiac rhythm variability and two-dimension echocardiography proved the importance of early postinfarction left ventricular dilatation in the onset of electrical cardiac instability, establishment of anatomic substrate of monomorphic ventricular tachycardias, low variability of cardiac rhythm. The findings evidence that MI patients with late ventricular potentials and end-diastolic left ventricular index above 100 ml/m2 in subacute period may be considered as a group of high risk in need of individual approach and further therapy. The discovered lowering of informative value of non-invasive methods in patients late after MI dictates the necessity of new approaches to detection of electrophysiological disturbances and sudden death risk in registration of postinfarction dilatation of the heart.     

Inhaled nitric oxide is not a myocardial depressant in a porcine model of heart failure

BACKGROUND: Inhaled nitric oxide has been shown to be a potent and selective pulmonary vasodilator. Reports of increases in left ventricular end-diastolic pressure and episodes of pulmonary edema during the clinical use of inhaled nitric oxide in patients with preexisting left ventricular dysfunction have raised concerns that this agent may have myocardial depressant effects. We therefore undertook a study of the effects of inhaled nitric oxide on myocardial contractility in a porcine model of ventricular failure and pulmonary hypertension. METHODS: After inducing heart failure in 10 pigs by rapid ventricular pacing, hemodynamic measurements and pressure-volume diagrams (by the conductance method) were obtained in six animals at baseline and during administration of inhaled nitric oxide at concentrations of 20 and 40 ppm. Myocardial contractile state was assessed by the end-systolic pressure-volume relationship and preload-recruitable stroke work, whereas diastolic function was measured in terms of the end-diastolic pressure-volume relationship and the pressure decay time constant T. RESULTS: Baseline hemodynamics reflected heart failure and pulmonary hypertension, and inhaled nitric oxide induced significant reductions in mean pulmonary artery pressure and pulmonary vascular resistance. Although left ventricular end-diastolic pressure increased during administration of inhaled nitric oxide, no changes were observed in measures of systolic or diastolic function. CONCLUSIONS: Inhaled nitric oxide reduced pulmonary vascular resistance but did not alter myocardial contractility or diastolic function. Increases in left ventricular end-diastolic pressure during inhaled nitric oxide therapy are therefore not due to myocardial depression and may be related to increases in volume delivery to the left side of the heart resulting from reduced pulmonary vascular resistance.     

The effect of L-DOPA on the motor activity of mouse fetuses

Most patients with acute myocardial infarction do not receive or are ineligible for thrombolytic therapy, and thus their prognosis is worse than that of the populations studied in the major, randomized, lytic therapy trials. We need to devise a cost-effective strategy with which to appropriately stratify these patients. Simple, easily ascertained clinical variables that are evident soon after hospital admission can identify higher-risk patients, who are likely to be older and less able to adequately complete an exercise test. In some patients, nuclear imaging tests are appropriate; low-dose dobutamine echocardiography and ambulatory ECG monitoring may also have a role. Greater use of routine cardiac catheterization (with assessment of ventricular function) might be the most appropriate way to stratify patients because it may overcome some of the limitations of noninvasive testing, will clearly define high-risk patients, and may facilitate early discharge from the hospital. Left ventricular function and the patency of the infarct-related artery will be determined, and patients with left main coronary disease, significant three-vessel coronary artery disease, and two-vessel coronary disease (especially with proximal left anterior descending coronary artery involvement) will be identified. An aggressive strategy of revascularization to improve survival in appropriate patients may be employed. Greater use of routine coronary arteriography after acute myocardial infarction would inevitably lower the threshold for inappropriate, potentially risky, and expensive further interventions. We need to focus our attention on the most appropriate strategies for the management of patients whose prognosis is worse than the prognosis of those who receive lytic therapy after acute myocardial infarction.     

Clinical and angiographic features of patients with an occluded versus a patent infarct vessel after intravenous streptokinase for acute myocardial infarction

Despite early treatment with thrombolytic agents for acute myocardial infarction, a significant portion of patients fail to achieve a patent infarct artery. To study the various factors related to achieving patency in the infarct vessel, 201 patients who received streptokinase within six hours of symptoms were studied. All patients underwent cardiac catheterization during the same hospitalization at 5.40 +/- 3.26 days after admission. Forty-five (22.4%) patients were found to have an occluded infarct artery (group 1) and 156 (77.6%) had a patent infarct vessel (group 2). There was no difference in the time from onset of symptoms to receiving streptokinase between the two groups. The two groups were similar to each other with regard to age, gender, history of myocardial infarction or angina, and major risk factors for coronary disease. Coagulation parameters before and after streptokinase therapy, reflecting the lytic state, were similar in both groups. The left ventricular end diastolic pressure was significantly higher and the left ventricular ejection fraction was significantly lower in group 1 than in group 2. These observations suggest that despite early initiation of thrombolytic therapy in patients with acute myocardial infarction, a significant portion of patients fail to achieve a patent infarct artery. This failure cannot be explained by the observed clinical parameters or the lytic state after streptokinase.     

Comparison of angiotensin converting enzyme and renin inhibition in rats following myocardial infarction

Renal and systemic hemodynamics were studied in rats 1 month after induction of myocardial infarction by ligation of the left coronary artery. The mean arterial pressure, heart rate, and cardiac index were not different from controls, but there were striking elevations in heart weight (p < 0.001), left ventricular end diastolic pressure (p < 0.002), and renal vascular resistance (p < 0.01). Renal blood flow and the percent of cardiac output perfusing the kidneys were reduced by 18% (p < 0.01) and 14% (p < 0.01), respectively. Acute angiotensin inhibition was studied at a dose of the converting enzyme inhibitor, enalapril, or the renin inhibitor, CP71362, that lowered the mean arterial pressure by 15 mm Hg in normal rats. In normal rats, enalapril and CP71362 were without effect on renal blood flow (RBF), renal vascular resistance (RR), and RBF as a percent of cardiac output. However, in rats with myocardial infarction, enalapril and CP71362 increased the RBF and RBF as a percent of cardiac output and lowered the RR to levels similar to normal controls (p < 0.02). Enalapril and CP71362 were equally effective in reducing the left ventricular end-diastolic pressure and total peripheral resistance in rats with myocardial infarction. These data demonstrate significant intrarenal vasoconstriction following myocardial infarction in the absence of detectable changes in mean arterial pressure or cardiac index. Converting enzyme inhibition or renin inhibition had similar beneficial effects on cardiorenal function, suggesting that both classes of compounds act by a similar mechanism to improve renal hemodynamics in congestive heart failure.     

Comparison of cardiovascular response to ionic and nonionic magnetic resonance susceptibility contrast agents

RATIONALE AND OBJECTIVES: Bolus injection of magnetic resonance (MR) contrast media has been used in recent years to exploit the diagnostic advantage of newer fast MR imaging sequences. The bolus effects of three equimolar dosages of ionic and nonionic magnetic susceptibility contrast agents on several cardiovascular functional parameters are investigated in normal rats and in rats subjected to acute myocardial infarction. These results are related to the osmolalities of the injected solutions. METHODS: Four groups of rats were examined (n = 10 rats per group). Twenty normal rats were studied. Acute myocardial infarction was produced by ligating the anterior branch of the left coronary artery for 2 hours in another 20 rats. Sequential equimolar doses of 0.1, 0.3, and 0.5 mmol/kg of ionic dysprosium diethylenetriamine pentaacetic acid dimeglumine ([NMG]2DyDTPA) or nonionic dysporosium diethylenetriamine pentaacetic acid-bis-methylamide (DyDTPA-BMA) (sprodiamide injection) were administered intravenously into the left jugular vein as a bolus. Hemodynamic parameters (heart rate, left ventricular pressures, rate of rise of left ventricular pressure [+/- dP/dt], and electrocardiogram as well as central and peripheral pressures) were continuously monitored for 15 minutes after each dose. Left ventricular developed pressure and rate pressure product, as indicators of myocardial oxygen consumption, were calculated. Osmolalities of the injected solutions were determined from freezing-point depression and correlated with the observed hemodynamic alterations. RESULTS: Bolus administration of 0.1, 0.3, and 0.5 mmol/kg DyDTPA-BMA produced no significant effect on the various hemodynamic parameters. (NMG)2DyDTPA caused dose-dependent attenuations in heart rate, left ventricular pressures, +/- dP/dt, rate pressure product and arterial blood pressures in both normal and infarcted rats. The magnitude of the response was dose dependent. Significant correlations were observed between osmolality and peak change of hemodynamic variables (r values between 0.99-1.00) after the administration of (NMG)2DyDTPA, but not after the injection of DyDTPA-BMA. CONCLUSIONS: Bolus administration of (NMG)2DyDTPA resulted in transient negative inotropic and chronotropic effects and hypotension in both healthy and infarcted animals. DyDTPA-BMA, administered as a bolus even at high doses, caused no appreciable hemodynamic alterations.     

Effects of brain death on myocardial function and ischemic tolerance of potential donor hearts

BACKGROUND: An increasing number of experimental and clinical studies reports hemodynamic instability in the donor organism after brain death. However, the relative importance of brain death-related cardiac dysfunction on posttransplantation cardiac function and the reversibility of the observed changes remain controversial. In this study a load-independent analysis of cardiac function after brain death was performed. Special interest was focused on a possible interactive influence of brain death and cardiac preservation on postischemic cardiac function. METHODS: In 12 anesthetized dogs, brain death was induced by inflation of a subdural balloon; 12 sham-operated animals served as control subjects. After a 2-hour observation in situ, the hearts were explanted and perfused parabiotically either immediately or after hypothermic ischemic preservation (4 hours, 4 degrees C). Heart rate, cardiac output, left ventricular pressure, the maximum of left ventricular pressure development and aortic pressure were measured in situ. In addition, the slope of the end-systolic pressure-volume relationship, coronary blood flow, and myocardial oxygen consumption were estimated in the cross-circulated hearts. RESULTS: In spite of a brain death-associated hemodynamic deterioration in situ (expressed as low mean aortic pressure and significant decrease of maximal dP/dt), myocardial function was similar to control after explantation, if assessed ex vivo. Furthermore, after hypothermic ischemic preservation and reperfusion, complete functional recovery of control and brain-dead hearts could be observed. CONCLUSIONS: These data indicate that hemodynamic instability after brain death may rather reflect altered loading conditions than irreversible myocardial damage or primary cardiac dysfunction. Furthermore, there is no evidence for a brain death-related impairment of ischemic tolerance.     

Importance of infarct-related artery patency for recovery of left ventricular function and late survival after primary angioplasty for acute myocardial infarction

OBJECTIVES: The purpose of this study was to evaluate the importance of late infarct-related artery patency for recovery of left ventricular function and late survival after primary angio-plasty for acute myocardial infarction. BACKGROUND: Infarct-related artery patency is thought to improve late survival by its effect on preservation of left ventricular function. Patency may also enhance late survival by preventing left ventricular dilation and reducing arrhythmias, independent of myocardial salvage. However, most studies have not shown patency to be an independent predictor of survival when late left ventricular function is taken into account. METHODS: We followed up 576 hospital survivors of acute myocardial infarction treated with primary angioplasty for 5.3 years. Ejection fraction and infarct-related artery patency were determined at follow-up catheterization at 6 months. Predictors of late cardiac survival were determined using Cox regression models. RESULTS: Patients with patent arteries had more improvement and a better late ejection fraction than patients with occluded arteries (56.3% vs. 47.9%, p = 0.001). In patients with acute ejection fraction < 45%, late survival was better in those with patent versus occluded arteries (89% vs. 44%, p = 0.003), but patency was not a significant predictor after improvement in ejection fraction was taken into account. In patients with a large anterior infarction, patency was a significant independent predictor of late survival. CONCLUSIONS: Infarct-related artery patency is important for recovery of left ventricular function, and in patients with acute ejection fraction < 45%, patency is important for late survival. Our data are consistent with the hypothesis that the survival benefit is due primarily to the effect of patency on recovery of left ventricular function. In patients with a large anterior infarction, patency appears to provide an additional late survival benefit independent of myocardial salvage. These observations support the need for additional clinical trials of late reperfusion in patients with a large anterior infarction.     

Left ventricular free wall rupture as the presenting manifestation of acute myocardial infarction in diabetic patients

We present 5 diabetic patients with acute myocardial infarction in whom left ventricular free wall rupture was the presenting manifestation. Echocardiography may be indicated in diabetic patients with acute myocardial infarction and in shock, prior to thrombolysis.     

Contractility changes of the right and ventricular muscle after chronic myocardial infarction

Contractility changes and adaptive responses resulting from acute left ventricular (LV) myocardial infarction are not restricted to the LV myocardium. The reduced LV function increased the right ventricular (RV) pressure load and neurohumoral factors, activated by the infarction     

The renin-angiotensin system in left ventricular remodeling

Left ventricular remodeling is a dynamic process that occurs in reaction to an insult to the myocardium. The response to either loss of cells, as may occur following myocardial infarction, or to hemodynamic overload, as may occur in aortic stenosis, is an attempt to maintain cardiac output and normalize wall tension. This is accomplished through the activation of the renin-angiotensin system and hypertrophy of noninfarcted segments of the myocardium. in the case of moderate or large infarctions these mechanisms fail to normalize wall stress. The stimulus to further remodeling remains, viable myocytes hypertrophy (with greater increases in cell length than width), the mass-to-volume ratio increases, and an exponential increase in wall stress results. This increase in myocyte tension has been associated with premature myocyte cell death. Thus, a vicious cycle is established wherein overstretch of the myocardium while sustaining cardiac output leads to progressive myocyte loss and left ventricular dilation. The renin-angiotensin system plays an integral role in this process. Its inhibition by angiotensin-converting enzyme (ACE) inhibitors both chronically and immediately after myocardial infarction has been shown to decrease left ventricular volumes and reduce mortality. Controversy exists regarding the mechanism through which ACE inhibitors exert their effects. ACE inhibitors reduce afterload/preload, circulating angiotensin II levels, and raise circulating levels of bradykinin. It is not yet clear which mechanism is responsible for the greatest impact on left ventricular dilation and mortality. inhibition of the renin-angiotensin system is clearly beneficial to cardiac performance as well as morbidity and mortality when myocardium is lost and heart failure ensues. Specific modes of action require further definition, including local and systemic effects. Possible benefits of angiotensin receptor blockade versus augmentation of bradykinin requires definition, setting the stage for further study, while the beneficial therapeutic use of these agents continues.