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Biomedical subjects

B I Jugdutt

Publications and source records attributed to B I Jugdutt.

At least 37 records · Page 2Linked to original sources
PubMed1998

Limitation of left ventricular hypertrophy and dysfunction by ACE inhibition after anterior Q-wave myocardial infarction.

To determine whether limitation of left ventricular (LV) hypertrophy with angiotensin-converting enzyme inhibition after myocardial infarction (MI) is associated with improved systolic and diastolic function, quantitative two-dimensional echocardiograms and Doppler of 40 patients, who were randomized on day 3 after a first Q-wave anterior MI to receive therapy with captopril (12.5 mg t.i.d.) or placebo for 6 weeks, were analyzed for LV volumes (Simpson's rule) and mass (3D reconstruction), remodeling parameters and peak early (E) and late (A) transmitral flow velocities and deceleration times (DT) at 3 days, 6 weeks, 6 months and 1 year. Compared to placebo over 1 year, captopril limited (p < 0.001) the increase in diastolic volume and mass, increased LV ejection fraction and diastolic E/A ratio, and decreased DT, the frequency of E and A reversal, infarct expansion and aneurysm frequency but volume/ mass ratio was unchanged. Captopril over the first 6 weeks after a first Q-wave anterior MI limited LV remodeling and hypertrophy and improved both systolic and diastolic function up to 1 year.

Analysis of Variance↗
PubMed1998

Effect of the novel angiotensin II type 1 receptor antagonist L-158,809 on acute infarct expansion and acute anterior myocardial infarction in the dog.

OBJECTIVES: To assess the effect of the angiotensin II type 1 receptor (AT1-R) antagonist L-158,809 on acute infarct expansion and left ventricular (LV) function during acute anterior myocardial infarction. METHODS: Dogs were randomized to receive intravenous L-158,809 (0.1 mg/kg bolus and 0.6 microgram/kg/min infusion) or vehicle beginning 1 h after permanent left anterior descending coronary artery ligation and continued for 48 h. In vivo LV remodelling and function (quantitative echocardiography) and hemodynamics over 48 h, and postmortem remodelling after 48 h were measured. RESULTS: L-158,809 produced 90% to 100% inhibition of the angiotensin II pressor response during the infusions. With respect to percentage changes over the 48 h in vivo, compared with vehicle controls, L-158,809 decreased mean arterial pressure (-20 +/- 4 versus -9 +/- 2%, P = 0.03) and left atrial pressure (-38 +/- 5 versus 25 +/- 6%, P < 0.0001) but did not change heart rate. These unloading effects were associated with a smaller percentage increase in infarct expansion index (-5 +/- 7% versus 27 +/- 2%, P = 0.001) and LV diastolic volume (11 +/- 11% versus 52 +/- 6%, P = 0.008), less shape deformation, fewer apical aneurysms (0 versus 100%, P = 0.0003), better global ejection fraction (49 +/- 2% versus 39 +/- 2%, P = 0.005), less ST segment elevation and fewer Q waves. Also compared with vehicle controls, with L-158,809 postmortem infarct size (19.8 +/- 2.4% versus 50.4 +/- 4.7% of risk region, P = 0.0002) and expansion index (2.06 +/- 0.09 versus 2.76 +/- 0.18, P = 0.006) were less and thinning ratio greater (0.92 +/- 0.02 versus 0.60 +/- 0.05, P = 0.0001). CONCLUSIONS: The novel AT1-R antagonist L-158,809 produces significant AT1-R blockade, reduces LV loading, and effectively limits acute infarct expansion and early LV remodelling during canine myocardial infarction.

Analysis of Variance↗
PubMed1997

Effect of reperfusion on ventricular mass, topography, and function during healing of anterior infarction.

The effect of reperfusion performed 2 h after left anterior descending coronary artery occlusion on in vivo changes (echocardiograms) in ventricular mass, topography, and function during postinfarction healing over 6 wk and postmortem topography (planimetry) and collagen (hydroxyproline) content at 6 wk were measured in dogs randomized to reperfusion (n = 12) and no reperfusion (n = 12). Compared with no reperfusion over the 6 wk, reperfusion resulted in less increase in systolic and diastolic volumes, less increase in ventricular mass, less infarct wall thinning, and mild improvement in global ejection fraction without any change in regional asynergy. Although reperfusion decreased the infarct collagen content at 6 wk, it reduced the in vivo expansion of the endocardial surface area; the elongation, diastolic bulge, echogenicity, and systolic thinning of the infarct zone; and the global shape index and aneurysm frequency. Thus reperfusion after 2 h attenuates regional and global dilation and produces less increase in mass during postinfarct healing than no reperfusion, so that the improvement in global systolic function cannot be attributed to global hypertrophy.

Animals↗
PubMed1997

Effect of angiotensin-converting enzyme inhibition on infarct collagen deposition and remodelling during healing after transmural canine myocardial infarction.

BACKGROUND: Angiotensin-converting enzyme (ACE) inhibition for six weeks after myocardial infarction (MI) lowers the collagen content of infarct scars in dogs. However, temporal changes in collagen content of the infarct zone (IZ) with ACE inhibition during healing over six weeks after MI and their possible relation to IZ remodelling have not been determined. METHODS: IZ collagen (hydroxyproline) was measured over six to seven weeks in dogs treated with captopril (50 mg bid), enalapril (2.5 mg bid) or placebo, beginning on the second day following transmural anterior MI (or sham). In vivo changes in IZ and global left ventricular (LV) remodelling, mass and function (echocardiograms) and hemodynamics among six-week survivors were also measured. RESULTS: Compared with placebo, both inhibitors decreased IZ collagen (P < 0.001) over the seven weeks. Among the six-week survivors, both inhibitors lowered IZ collagen (P < or = 0.001) and increased the collagen type I:III ratio. However, preload was lower, increase in diastolic volume and mass were less and systolic function improved. Although the doses of captopril (but no enalapril) decreased afterload, inhibition of IZ collagen was less, IZ bulging and global LV dilation were less and systolic function was better with captopril than with enalapril. In all three MI groups, deaths over the seven weeks correlated with greater infarct size, LV volume and dysfunction and lower IZ collagen. CONCLUSIONS: ACE inhibition suppresses the temporal increase in IZ collagen and attenuates IZ expansion, thinning and bulging, and LV enlargement and aneurysm formation during healing after MI.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1997

Changes in myocardial density during postinfarction healing: effect on estimation of in vivo left ventricular mass by echocardiographic imaging.

To determine whether changes in density (rho) of infarct and noninfarct zones during healing and remodeling after myocardial infarction influence estimates of left ventricular mass and detection of temporal changes by imaging, we measured weights (g) and volumes (mL) of infarct, noninfarct, and mixed tissue in hearts removed 1 to 42 days after anterior infarction in three groups of dogs: nonreperfused infarction treated with placebo or captopril, or infarcts reperfused after 2 h. In vivo mass was calculated from in vivo diastolic myocardial volumes (echocardiograms) and an assumed density of 1.05 g/mL or actual values derived from tissue weights and volumes. Over the 42 days, actual density deviated more from the assumed value of 1.05 in infarct than noninfarct zones, and the overall density was higher for reperfused than nonreperfused ventricles (1.09 vs. 1.06 g/mL, p < 0.01). Correction for density improved the correlation between absolute in vivo and postmortem mass slightly but not the detection of relative changes in mass in control, captopril, or reperfusion groups. These findings suggest that (i) densities of infarct and noninfarct zones differ and change during healing, especially after reperfusion, and (ii) correction for density provides more accurate estimates of volume-derived mass in reperfused hearts.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1997

Effects of amlodipine versus enalapril on left ventricular remodelling after reperfused anterior myocardial canine infarction.

OBJECTIVE: To compare the effects of the calcium channel blocker amlodipine with those of the angiotensin-converting enzyme (ACE) inhibitor enalapril on left ventricular (LV) remodelling and dysfunction during healing after reperfused anterior myocardial infarction (MI). ACE inhibitors and reperfusion are known to limit LV remodelling after MI. However, the effects of ACE inhibitors and calcium channel blockers on LV remodelling after reperfused MI have not been compared. METHODS: Changes in LV topography and function (quantitative echocardiograms) and hemodynamics were measured over six weeks in dogs that were randomized 24 h after reperfusion, done after 2 h of anterior MI, to oral amlodipine (5 mg bid; n = 7), enalapril (5 mg bid; n = 6) or no drug (controls; n = 6) for six weeks. Postmortem LV topography was measured at six weeks. RESULTS: Scar sizes after six weeks were similar in the three groups. Both enalapril and amlodipine reduced the rate pressure product, but decreases in mean arterial and left atrial pressures were more sustained over six weeks with enalapril. Compared with controls over six weeks, both enalapril and amlodipine preserved LV volumes, global ejection fraction, regional function and infarct segment length, but enalapril blocked the increase in non-infarct wall thickness, attenuated the infarct wall thickness, preserved shape and decreased global LV mass more than amlodipine. Sham-operated dogs (n = 3) showed no significant structural changes. CONCLUSIONS: Both enalapril and amlodipine preserve LV volumes and function during healing after reperfused MI, but enalapril more effectively limits hypertrophy, attenuates infarct wall thickness and preserves shape.

Amlodipine↗
PubMed1996

Opposite effects of angiotensin AT1 and AT2 receptor antagonists on recovery of mechanical function after ischemia-reperfusion in isolated working rat hearts.

BACKGROUND: Angiotensin II type 1 (AT1) receptor antagonists, when given over the long term, reduce the deleterious consequences of ischemia-reperfusion injury. Whether short-term administration of AT1 or angiotensin II type 2 (AT2) receptor antagonists is cardioprotective has not been investigated. METHODS AND RESULTS: The effects of short-term administration of selective AT1 and AT2 receptor antagonists on the recovery of mechanical function during reperfusion after 30 minutes of global, no-flow ischemia were studied in left atrium-perfused isolated working rat hearts. Control hearts (n = 8) showed incomplete recovery of left ventricular minute work (LV work) and cardiac efficiency during reperfusion to 51 +/- 15% and 61 +/- 19% of preischemic levels, respectively. Compared with control hearts, the selective AT2 receptor antagonist PD123,319 (0.3 mumol/L) given before ischemia (n = 7) improved the recovery of LV work and efficiency to 82 +/- 4% and 98 +/- 7% of preischemic levels, respectively (P < .01). In contrast, the selective AT1 antagonist losartan (1 mumol/L) blocked the recovery of LV work and depressed efficiency to 0 +/- 0% and 1 +/- 0% (n = 7) of preischemic levels, respectively (P < .01; n = 7). Neither antagonist altered coronary vascular conductance. CONCLUSIONS: This is the first demonstration that short-term treatment with a selective AT1 versus AT2 antagonist exerts different effects on recovery of mechanical function after ischemia-reperfusion: the AT2 antagonist was cardioprotective, whereas the AT1 antagonist was not. These data suggest that AT2 antagonists and AT1 agonists may offer novel approaches for the treatment of mechanical dysfunction after ischemia-reperfusion.

Angiotensin Receptor Antagonists↗
PubMed1996

Rate of collagen deposition during healing and ventricular remodeling after myocardial infarction in rat and dog models.

BACKGROUND: We hypothesized that the rate and amount of infarct collagen deposition during healing after myocardial infarction might influence ventricular remodeling in rat and dog models. The purpose of this study was to compare rates of infarct collagen deposition and ventricular remodeling in the two models. METHODS AND RESULTS: Infarcted rat and dog hearts were removed at fixed time intervals between 1 and 50 days for measuring remodeling parameters and infarct and noninfarct collagen content (mg/g hydroxyproline). Collagen was less in sham rat (n=29) than dog (n=30) ventricles (3.32 versus 4.57 mg/g, P<.001) and markedly lower in the rat (n=48) than dog (n=59) infarcts throughout healing and by 50 days (9.98 versus 56.74 mg/g, P<.0001). Infarct collagen leveled off earlier and healing (histology) was completed sooner in the rat. Infarct scars were also thinner in the rat, with more (P<.0001) thinning and bulging (mm/g), and greater increase in ventricular volume. Although the mass to volume ratio decreased (P<.001) in both models, global remodeling was different, with greater transverse axis widening and globularity in the dog. Although infarct size, transmurality, heart rate, filling pressure, and blood pressure were greater in the rat, infarcts 10% to 30% in size in both models showed similar differences in infarct collagen and remodeling. CONCLUSIONS: Compared with dog infarcts, rat infarcts exhibited faster healing and infarct collagen deposition and markedly lower infarct collagen. In addition to larger, more transmural, and thinner infarcts, and greater hemodynamic load, the lower infarct collagen in that model might be an important factor in the greater regional remodeling.

Animals↗
PubMed1996

Effect of nitrates on myocardial remodeling after acute myocardial infarction.

Nitrates are effective for the therapy of acute coronary syndromes, including acute myocardial infarction. Their application in acute infarction has established that vasodilators are beneficial provided hypotension is avoided. Nitrates limit early ventricular remodeling in infarction. New dosing strategies and formulations that permit chronic use after infarction with less tolerance might limit late remodeling. Over the last decade, the demonstrated effectiveness of angiotensin-converting enzyme (ACE) inhibitors in limiting ventricular dilation postinfarction has generated controversy over the usefulness of nitrates for that indication. The uncertainty has been intensified by 2 large mortality trials that tested both agents as adjuncts to conventional therapy. These trials were not designed to test whether nitrates might limit remodeling. Mechanistic experimental and clinical studies that tested whether nitrates or ACE inhibitors could effectively limit ventricular remodeling showed that both improved remodeling endpoints. However, experimental studies raise some concern about the decrease in infarct collagen associated with ACE inhibition and emphasize the fact that final outcome represents a balance of effects. That nitrates do not decrease infarct collagen could be important. Nitrate-induced early recruitment of ventricular function after late reperfusion of acute infarction might also be important. In the mortality trials, >50% of patients received open-label nitrates as per indication. Thus, the trial results to date do not suggest that nitrates are ineffective for remodeling, but rather that ACE inhibitors can confer added benefit. There has been no large clinical trial to test the efficacy of nitrates for remodeling as there has been for ACE inhibitors.

Animals↗
PubMed1996

Effect of prolonged inotropic stimulation on ventricular remodeling during healing after myocardial infarction in the dog: mechanistic insights.

OBJECTIVES: We hypothesized that positive inotropic stimulation during healing after myocardial infarction might increase contractile pull on the infarct segment, increase expansion and promote ventricular dilation. BACKGROUND: The effect of prolonged inotropic stimulation on left ventricular remodeling during healing after myocardial infarction has not been studied. METHODS: The effects of 6 weeks of inotropic stimulation on in vivo changes in left ventricular topography, function and mass (serial two-dimensional echocardiograms), hemodynamic variables, postmortem topography (planimetry) and collagen (hydroxyproline content) were studied in 36 chronically instrumented dogs randomized, 2 days after small anterior infarction, to digoxin (0.125 mg daily) and no digoxin (control group). RESULTS: Heart rate and arterial and left atrial pressures were similar in the two groups, but the first derivative of left ventricular pressure (peak dP/dt), systolic thickening of the noninfarct wall and systolic thinning of the infarct wall were higher in the digoxin group during the 6 weeks. At 6 weeks, infarct scar size and collagen content were similar in both groups, but the digoxin group had more infarct expansion and thinning. Between 2 days and 6 weeks, the digoxin group showed more in vivo diastolic infarct expansion, thinning and bulging; more aneurysm but less global dilation and increase in mass; and no change in ejection fraction. The effects of inotropic stimulation on remodeling were more marked in infarcts with 100% than 85% transmurality. CONCLUSIONS: Prolonged inotropic stimulation with digoxin during healing after small anterior infarction increases infarct bulging without decreasing infarct collagen content and preserves global ventricular size, mass and systolic function.

Animals↗
PubMed1995

Impact of left ventricular unloading after late reperfusion of canine anterior myocardial infarction on remodeling and function using isosorbide-5-mononitrate.

BACKGROUND: Late reperfusion during acute myocardial infarction results in delayed recovery of ventricular function and less remodeling, whereas ventricular unloading with nitrates improves function and attenuates remodeling. Whether late reperfusion combined with prolonged unloading with isosorbide-5-mononitrate (ISMN) might produce greater functional recovery and less remodeling than late reperfusion alone is not known. METHODS AND RESULTS: In vivo left ventricular function and topography (echocardiograms), postmortem topography (planimetry), and collagen (hydroxyproline) were measured in dogs that were randomized to reperfusion 2 hours after left anterior descending coronary artery ligation, and ISMN (n = 12) or placebo (n = 12) was given as 25 mg IV over 4 hours followed by 50 mg PO QID for 6 weeks. Compared with placebo, the ISMN group had similar heart rate but lower left atrial pressure, mean arterial pressure, and rate-pressure products. Although in vivo baseline remodeling and functional parameters were similar in the two groups, by 6 weeks the ISMN group had smaller (P < or = .05) infarct and noninfarct segment lengths, ventricular volumes, and mass; less (P < .001) asynergy; and greater (P < .001) ejection fraction. More important, by 2 days, ejection fraction was 18% greater (P < .025) and asynergy 26% less (P < .05) with ISMN. At 6 weeks, ISMN showed less (P < or = .05) scar size, scar collagen, cavity dilation, noninfarct wall thickness, and apical bulging than placebo. In another 4 dogs, acute ISMN produced less improvement in function and remodeling than prolonged ISMN. CONCLUSIONS: Late reperfusion of acute anterior myocardial infarction combined with prolonged ISMN unloading results in greater and earlier recovery of ventricular function and less remodeling than late reperfusion alone.

Animals↗
PubMed1995

Effect of enalapril on ventricular remodeling and function during healing after anterior myocardial infarction in the dog.

BACKGROUND: Ventricular remodeling after myocardial infarction involves changes in ventricular size, shape, structure, and matrix that impact on function. Prolonged angiotensin-converting enzyme inhibition after infarction with captopril reduces ventricular enlargement and improves clinical outcome, but whether enalapril produces similar benefits is controversial. METHODS AND RESULTS: The effect of enalapril during healing between 1 day and 6 weeks after myocardial infarction on in vivo changes in ventricular size, shape, mass, and function (asynergy, or akinesis and dyskinesis, and ejection fraction), as determined by serial two-dimensional echocardiography, hemodynamics, postmortem topography (planimetered short- and long-axis ventricular contours), and collagen content (determined by levels of hydroxyproline, a marker for collagen), was measured in 25 instrumented dogs. The dogs were randomized 1 day after left anterior descending coronary artery ligation to a control group (no treatment) and a group receiving oral enalapril (2.5 mg BID). Compared with no treatment, enalapril produced a sustained lowering of left atrial pressure but no difference in heart rate and mean blood pressure over the 6 weeks. Also compared with no treatment, enalapril modified in vivo remodeling parameters between 1 day and 6 weeks, with less elongation of the asynergy-containing segment, a lower expansion index (ratio of endocardial lengths of infarct to non-infarct-containing segments demarcated by papillary muscle landmarks), less scar wall thinning, a lower thinning ratio (ratio of average thickness of infarcted wall to average thickness of the normal wall), smaller ventricular volume, less regional bulging and aneurysm frequency, prevention of the increase in ventricular mass, less total extent of asynergy, and higher volume ejection fraction. At postmortem examination, scar mass was similar in the two groups, but topographic maps with enalapril revealed less infarct bulging, flatter infarct scars, and less noninfarct wall thickness. In addition, postmortem collagen content was similar in noninfarct zones of the two groups but lower in infarct zones of the dogs given enalapril. CONCLUSIONS: Prolonged enalapril therapy, in a dose that did not lower blood pressure, during healing after anterior infarction produced prolonged reduction of left ventricular preload in dogs. This diastolic unloading was associated with limitation of remodeling parameters (infarct expansion and thinning, progressive ventricular dilation and hypertrophy, and regional bulging), less total asynergy, and improved left ventricular ejection fraction. Although angiotensin-converting enzyme inhibition was associated with lower collagen content in the infarct area and altered scar topography, these effects did not impact negatively on overall remodeling and function.

Aldosterone↗
PubMed1995

Laser-induced fluorescence: III. Quantitative analysis of atherosclerotic plaque content.

BACKGROUND AND OBJECTIVE: Laser-induced fluorescence (LF) spectroscopic analysis of the chemical composition of atherosclerotic plaque was examined. STUDY DESIGN/MATERIALS AND METHODS: The intima of 18 dog aortas was injected with chemical compounds found in atherosclerotic plaque. Spectra were recorded in air prior to and after injection of collagens I, III and IV, elastin, cholesterol, triglyceride, and beta-nicotinamide adenine dinucleotide (NADH). RESULTS: Significant changes in LF intensity were detected after injection of collagens I and III, cholesterol and elastin in thoracic aorta (P < 0.001), but not with triglyceride or NADH. Minor changes were detected in abdominal aorta. Multiple regression analysis of LF intensity ratios demonstrated a clear correlation with the quantity of injected collagens I (R2 = 0.90-0.99) and III (R2 = 0.84-1.0), cholesterol (R2 = 0.72-0.76), and triglyceride (R2 = 0.68-0.80) in both thoracic and abdominal aorta. The correlation between LF and atherosclerotic plaque composition was confirmed in a rooster model of atherosclerosis where multiple regression analysis predicted the measured aortic cholesterol (R2 = 0.78) and triglyceride content (R2 = 0.96). CONCLUSIONS: (1) Fluorescence spectra recorded from dog aorta were significantly altered by injection of collagens I and III, cholesterol, and elastin. (2) LF may allow quantitative assessment of plaque chemical content.

Analysis of Variance↗
PubMed1995

Combined captopril and isosorbide dinitrate during healing after myocardial infarction. Effect on ventricular remodeling, function, mass and collagen.

OBJECTIVES: We sought to compare the effects of captopril plus isosorbide dinitrate versus monotherapy on infarct collagen content and left ventricular remodeling and function during healing after myocardial infarction. BACKGROUND: Captopril or isosorbide dinitrate monotherapy can limit postinfarction dilation. Whether captopril inhibits infarct collagen content, or whether captopril plus isosorbide dinitrate might be more beneficial, is not known. METHODS: In vivo remodeling variables and function (echocardiography), hemodynamic variables, postmortem topography (planimetry) and collagen content (hydroxyproline) were measured in 48 chronically instrumented dogs that were randomized 2 days after left anterior descending coronary artery ligation to 6 weeks of therapy with captopril, isosorbide dinitrate, captopril plus isosorbide dinitrate or placebo. RESULTS: Compared with placebo, the three active therapies decreased blood pressure and left atrial pressure; limited infarct expansion, infarct thinning, noninfarct wall stretching and thickening; limited left ventricular dilation and increase in left ventricular mass; and decreased regional bulging, aneurysm frequency and left ventricular dysfunction. However, the decrease in asynergy and increase in volume ejection fraction were less with captopril or captopril plus isosorbide dinitrate than with isosorbide dinitrate. Infarct thinning and bulging at 6 weeks was also less with isosorbide dinitrate than with captopril. Although initial left ventricular asynergy, final scar sizes and noninfarct collagen content at 6 weeks were similar among the groups, collagen in the center of the infarct scar was less with captopril or captopril plus isosorbide dinitrate than with placebo or isosorbide dinitrate. CONCLUSIONS: Monotherapy with captopril or isosorbide dinitrate, or their combination, improved all remodeling variables, but isosorbide dinitrate improved function more than captopril or captopril plus isosorbide dinitrate. Inhibition of infarct collagen content by captopril suggests that benefits with captopril represent a balance between positive and negative effects, and its combination with isosorbide dinitrate might be advantageous.

Animals↗
PubMed1995

Effect of captopril and enalapril on left ventricular geometry, function and collagen during healing after anterior and inferior myocardial infarction in a dog model.

OBJECTIVES: This study compared the effects of captopril and enalapril on left ventricular geometry, function and mass and on scar collagen and topography during healing after anterior and inferior myocardial infarction in a canine model. BACKGROUND: The beneficial effect of prolonged angiotensin-converting enzyme inhibitor therapy on remodeling during healing after myocardial infarction might be greater in anterior than inferior infarcts and more effective with captopril than enalapril therapy. METHODS: The effects of 6 weeks of therapy with captopril (50 mg twice a day), enalapril (2.5 mg twice a day) or placebo on in vivo variables of left ventricular remodeling, function and mass (by echocardiography), hemodynamic function, postmortem topography (by planimetry) and collagen (hydroxyproline levels) were studied in 36 instrumented dogs randomized to receive therapy 48 h after left anterior descending or left circumflex coronary artery occlusion. RESULTS: Compared with placebo therapy, both captopril and enalapril decreased infarct expansion and thinning, progressive ventricular dilation, ventricular mass and asynergy and infarct collagen levels in anterior and inferior infarcts. Despite similar small scar sizes, the effects on remodeling and dysfunction were greater in anterior than inferior infarcts. In addition, captopril produced greater attenuation of infarct expansion and ventricular enlargement, greater improvement in volume ejection fraction and less decrease in infarct collagen levels than enalapril. CONCLUSIONS: On balance, captopril and enalapril attenuated left ventricular remodeling and preserved function in small anterior and inferior infarcts despite differences in the effects of the drugs on individual remodeling variables. Further studies will be needed to determine whether inhibition of infarct collagen might be harmful, or differences between captopril and enalapril therapy important, in large transmural infarctions.

Animals↗
PubMed1994

Nitrates in myocardial infarction.

Until two decades ago nitroglycerin was contraindicated in acute myocardial infarction (MI). Studies in the canine model demonstrated that low-dose intravenous (i.v.) infusion, carefully titrated to decrease mean blood pressure by 10% but not below 80 mmHg, during early stages of acute MI produced marked reduction of left ventricular (LV) preload, improvement in regional perfusion, and limitation of infarct size and remodeling. However, more i.v. nitroglycerin to decrease blood pressure further resulted in a paradoxical J-curve effect, with hypoperfusion and increased infarct size. Clinical studies have confirmed that low-dose i.v. nitroglycerin infusion for the first 48 hours after acute MI is safe, not only for improving performance in LV failure, but also for limiting ischemic injury, infarct size, remodeling, and infarct-related complications, including deaths in-hospital and up to 1 year. Recent studies suggest that more prolonged therapy with nitrates spanning the healing phase of acute anterior Q-wave MI can further limit LV remodeling and preserve function. Preliminary results of the recently completed ISIS-4 megatrial suggest, however, that long-term nitrate in patients with suspected MI in the 1990s does not improve survival significantly.

Animals↗
PubMed1994

Use of nitroglycerin for the treatment of acute myocardial infarction.

After a decade of warnings against the use of nitrates in acute myocardial infarction (MI), they are becoming recognized for their potential to salvage left ventricular (LV) myocardium, geometry and function. Low-dose intravenous (IV) nitroglycerin (NTG) infusion for the first 48 h after acute MI, titrated to lower mean blood pressure by 10% to 30%, but not below 80 mmHg, has been shown to be safe, to improve hemodynamics, and to decrease infarct size, infarct expansion, complications, and deaths in a prospective, randomized, single-blind study of 310 patients. In addition, low-dose NTG infusion for the first 48 h, followed by prolonged buccal NTG given during healing after acute MI in an eccentric dose schedule to minimize tolerance, was found to limit further progressive remodeling and preserve LV function. Meta-analysis of nitrate studies in acute MI indicate that they improve survival. Preliminary and ongoing studies suggest that prolonged NTG therapy post MI can produce further benefit.

Humans↗