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Biomedical subjects

P F Cohn

Publications and source records attributed to P F Cohn.

At least 19 recordsLinked to original sources
PubMed1998

Maximizing the hemodynamic benefit of enhanced external counterpulsation.

BACKGROUND: Enhanced external counterpulsation (EECP) has been demonstrated to be an effective treatment for angina and exertional ischemia in patients with coronary disease. HYPOTHESIS: It is hypothesized that the ability of EECP to enhance the recruitment or development of coronary collaterals in coronary artery disease may be determined by the relative magnitude of diastolic augmentation (DA) and systolic unloading (SU). This study examines the relation between the proposed EECP effectiveness ratio (DA/SU), as assessed by finger plethysmography, and changes in descending aortic flow as assessed by Doppler echocardiography in 15 patients during EECP. METHODS: Varying external cuff pressures (0-275 mmHg) were used to generate a range of DA/SU ratios. The effect on aortic antegrade systolic and retrograde diastolic flow was assessed by Doppler echocardiography to determine whether there was an optimal EECP effectiveness ratio that maximizes the hemodynamic effects of EECP. With increasing DA/SU there was an initial positive linear increase in both systolic and diastolic flow volume. Systolic flow maximized at an effectiveness ratio of 1.5 and diastolic flow at a ratio of 2.0 RESULT: Therefore, effectiveness ratios (DA/SU) in the range of 1.5-2.0 are optimal for maximizing the hemodynamic effects of EECP.

Adult↗
PubMed1998

Prior revascularization increases the effectiveness of enhanced external counterpulsation.

BACKGROUND AND HYPOTHESIS: Enhanced external counterpulsation (EECP) is an effective noninvasive treatment for chronic angina. However, its usefulness has been felt to be limited in patients with angiographically demonstrated triple-vessel coronary artery disease (CAD), in accord with the hypothesis that a patent vessel is necessary for transmission of the EECP-augmented coronary artery pressure and volume to the distal coronary vasculature. METHODS: The effect of revascularization [coronary artery bypass grafting (CABG)] prior to EECP was examined in 60 patients with CAD and chronic angina (35 without and 25 with prior CABG). Patients were grouped by the extent of CAD (single-, double-, triple-vessel disease in the unrevascularized group) and by the extent of residual disease (number of stenotic native vessels unbypassed or supplied by a stenotic graft in the CABG group). Significant CAD or graft stenoses were defined as stenoses demonstrating > or = 70% luminal diameter narrowing. Benefit was assessed by improvement in post-EECP treatment over pretreatment radionuclide stress testing. RESULTS: Radionuclide stress testing demonstrated a comparable favorable response (80 vs. 71%; p = NS) in patients with prior CABG versus unrevascularized patients. Enhanced external counterpulsation was highly and comparably effective in patients with unrevascularized native single- and double-vessel CAD and in patients with CABG with residual single- and double-vessel CAD (88 vs. 80%; p = NS). Most notably, CABG significantly increased the beneficial response to EECP in those patients with triple-vessel CAD and stenotic grafts compared with unrevascularized patients with triple-vessel CAD (80 vs. 22%; p < 0.05 by chi-square test). CONCLUSION: The results suggest a new role for EECP as an effective treatment for post CABG ischemia, despite extensive CAD and even in the presence of stenotic grafts.

Aged↗
PubMed1998

Treatment of chronic myocardial ischemia: rationale and treatment options.

A rational approach to the treatment of chronic myocardial ischemia requires an appreciation of the pathophysiology of coronary artery disease and the treatment options available. Any factor that causes an imbalance between myocardial oxygen supply and demand can provoke ischemia. Myocardial oxygen requirements rise with increases in heart rate, contractility, or left ventricular wall stress. Myocardial oxygen supply is determined by coronary artery flow and myocardial oxygen extraction. Anti-anginal medications are the mainstay of anti-ischemic management and act to correct the balance between myocardial supply and demand by increasing coronary blood flow, reducing myocardial oxygen requirements, or both. These medications include nitrates (which act principally by venous vasodilation, but also probably by coronary dilation), beta-blockers (which act mainly by reducing heart rate and cardiac contractility), and calcium channel blockers (which act principally by arterial and coronary vasodilation). The choice of therapy and its effectiveness depend on the underlying cause of ischemia. The complimentary mechanisms of action of these drug classes suggest that their use in combination may result in a greater reduction in myocardial oxygen demand than that achieved with monotherapy. In addition, the pharmacological actions of some of these drugs may serve to offset the undesirable side effects associated with others, for example, the reflex tachycardia produced by some calcium channel blockers may be offset by beta-blocker therapy. Finally, aspirin and lipid-lowering drugs and the potential role for anti-oxidants must also be considered in combination therapy. Invasive techniques for myocardial ischemic management, such as coronary artery bypass and coronary angioplasty, improve myocardial oxygen supply by relieving or circumventing the atherosclerotic obstruction responsible for ischemia. Surgery is the preferred technique in patients with certain medical conditions, for example, those with triple-vessel disease, but is not recommended in patients with mild angina unless left main artery disease is present.

Animals↗
PubMed1997

Enhanced external counterpulsation as an adjunct to revascularization in unstable angina.

Enhanced external counterpulsation (EECP) is an effective noninvasive treatment for chronic stable angina. Despite intensive risk factor modification, a patient required two surgical coronary revascularizations and seven multivessel angioplasties over a 26-month period, demonstrating recurrent unstable angina and persistent thallium perfusion defects despite revascularization. Post EECP, angina was relieved, thallium defects were resolved and the patient has remained asymptomatic for 36 months.

Angina, Unstable↗
PubMed1997

Rationale for the use of calcium antagonists in the treatment of silent myocardial ischemia.

Silent myocardial ischemia, whether it occurs at rest or during exercise, is associated with an unfavorable prognosis and may lead to sudden cardiac death. Agents used to treat silent myocardial ischemia have included nitrates, beta-blockers, and calcium antagonists (CAs). Despite treatment with traditional anti-ischemic agents, studies have shown that up to 40% of patients who receive what is considered to be clinically optimal antianginal therapy continue to have daily episodes of silent myocardial ischemia. The use of nitrates and beta-blockers is sometimes confounded by issues of tolerance and tolerability. Although the CAs have been found to be effective in decreasing the duration and frequency of episodes of silent ischemia, in general beta-blockers produce a greater reduction in these variables. Thus a need for effective and tolerable anti-ischemic agents persists. A new class of CAs, the tetralol derivatives, may show promise in this regard. The first of this new class, mibefradil, is characterized by selective blockade of T-type calcium-ion channels and has been shown in a few studies to reduce the frequency and duration of asymptomatic ischemic episodes in patients with stable exertional angina pectoris. Large-scale clinical trials are necessary before the efficacy and tolerability of this new CA can be compared fully with those of the beta-blockers and currently available CAs.

Adrenergic beta-Antagonists↗
PubMed1997

Pharmacological treatment of ischaemic heart disease. Monotherapy vs combination therapy.

Non-invasive treatment continues to be the mainstay of anti-ischaemic therapy. The imbalance between myocardial oxygen supply and demand provides the basis for myocardial ischaemia, which may present as symptomatic, asymptomatic or, in most cases, a mixture of the two. Both symptomatic and silent ischaemia are major prognostic indicators in patients with coronary artery disease and treatment should therefore be directed towards both the amelioration of symptoms and the resolution of the signs of ischaemia. Anti-ischaemic therapy may decrease oxygen demand, increase myocardial oxygen supply, or both. Interventional therapies, such as percutaneous transluminal coronary angioplasty and bypass grafting, improve supply but do not alter demand. Drug therapy is associated with a variety of effects upon both supply and demand, depending upon the agent used. Nitrates alter both myocardial oxygen supply and demand, while beta-blockers decrease myocardial oxygen demand. Calcium channel blockers reduce after load and myocardial contractility and, thus, lower oxygen demand, while the coronary artery relaxation that occurs in response to their use acts to increase supply. The use of combination therapy is considered by many to be the most rational approach to the treatment of myocardial ischaemia, in that it allows maximal reduction in demand and increase in supply.

Adrenergic beta-Antagonists↗
PubMed1996

Can angiographic findings predict which coronary patients will benefit from enhanced external counterpulsation?

Enhanced external counterpulsation is an effective treatment for chronic angina. Theoretical considerations predict greatest benefit in patients with at least 1 patent conduit in this group of 50 patients (all of whom improved clinically). Improvement in radionuclide stress perfusion imaging was seen in 80% of treated patients and was inversely related to extent of coronary disease.

Aged↗
PubMed1994

Silent myocardial ischemia: to treat or not to treat?

The risk of infarction and sudden death is considerable in patients with silent ischemia, whether it occurs alone or is interspersed with episodes of angina. The ischemic activity can be modified or even abolished, most effectively with beta-blocker and nitrate therapy. But it is not yet clear whether treatment improves outcome, although the limited available data suggest that it does.

Adrenergic beta-Antagonists↗
PubMed1994

Concomitant use of nitrates, calcium channel blockers, and beta blockers for optimal antianginal therapy.

Despite the introduction of new mechanical techniques for revascularization, pharmacologic therapy continues to be the mainstay of antianginal therapy. The conventional antianginal medications, which include nitrates, beta blockers, and calcium channel blockers, act to correct the imbalance between myocardial supply and demand by increasing coronary blood flow, reducing myocardial oxygen requirements, or both. All three are appropriate for the management of angina caused by a fixed coronary obstruction, but nitrates and calcium channel blockers, which not only reduce demand but also increase supply, are preferred in cases of angina believed to involve a significant increase in vasomotor tone. Because of the different yet complementary mechanisms of action of the three classes of anti-ischemic drugs, use of these agents in combination is a rational approach to the treatment of angina unresponsive to monotherapy. Such combinations have been shown to enhance the therapeutic response achieved with single-agent therapy. In addition, the pharmacologic action of one of the components of the combination regimen may serve to offset side effects typically associated with the other.

Adrenergic beta-Antagonists↗
PubMed1994

Effects of captopril therapy after late reperfusion on left ventricular remodeling after experimental myocardial infarction.

Reperfusion that is too late to salvage ischemic myocardium reduces early infarct expansion, and captopril therapy favorably alters long-term left ventricular remodeling. To study whether the beneficial effects of these two therapies are additive, we examined the effects of captopril therapy after late reperfusion on left ventricular remodeling after acute myocardial infarction. Female Sprague-Dawley rats (n = 67) were randomly assigned to one of four groups: group 1, sham surgery and no treatment; group 2, left coronary artery ligation and no treatment (myocardial infarction [r MI]); group 3, left coronary artery ligation, reperfusion 2 hours later, and no treatment (late reperfusion [LR]); and group 4, left coronary artery ligation, reperfusion 2 hours later, and captopril treatment (LR-Cap). Captopril therapy (2 gm/L of drinking water) was begun in the LR-Cap group in the immediate post-operative period and continued for 20 days. Twenty-one days postoperatively, hemodynamic measurements were made before and after volume loading. The rats were killed, their hearts were removed, and passive pressure-volume curves were obtained. The hearts were then fixed at a constant pressure for morphometric analysis. Compared with the MI group, the LR group had a lower expansion index and a higher thinning ratio. There were no differences in hemodynamics, left ventricular volumes, or other morphometric indexes between the two groups. Compared with the MI and LR groups, the LR-Cap group had lower peak left ventricular end-diastolic pressure, lower left ventricular volume, lower left and right ventricular weights, and a leftward shift of pressure-volume curves.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Effects of metoprolol on early infarct expansion after acute myocardial infarction.

The effects of metoprolol on early infarct expansion after acute myocardial infarction were studied in rats (n = 54) that underwent either left coronary artery ligation (MI) or sham operation. Immediately after surgery, the rats received either metoprolol (M) by mouth, which had been dissolved in drinking water, for 72 hours supplemented with three intraperitoneal doses over the first 24 hours or no treatment (H2O). Three days after the initial surgery, hemodynamic measurements were made before and after volume loading. The rats were killed, the hearts were removed, and passive pressure-volume curves were obtained. The hearts were then fixed at a constant pressure and analyzed morphometrically. Infarct size was nonsignificantly lower in the metoprolol-treated group compared with the untreated group (38% +/- 5% MI-M vs 48% +/- 3% MI-H2O, p = 0.10) Compared with infarcted untreated rats, infarcted metoprolol-treated rats had a lower heart rate (322 +/- 13 beats/min MI-M vs 452 +/- 19 beats/min MI-H2O, p < 0.001), lower left ventricular systolic pressure (63 +/- 4 mm Hg MI-M vs 90 +/- 6 mm Hg MI-H2O, p = 0.004), and lower +dp/dt (1340 +/- 169 mm Hg/sec MI-M vs 2872 +/- 273 mm Hg/sec MI-H2O, p < 0.001), but left ventricular end-diastolic pressure and cardiac index did not differ between the two groups. Left ventricular weight corrected for body weight was higher in infarcted rats treated with metoprolol compared with infarcted untreated rats (2.76 +/- 0.07 gm/kg MI-M vs 2.41 +/- 0.09 gm/kg MI-H2O, p < 0.05). The initial slope of the pressure-volume relationship Ki, an index of operative volume stiffness, was lower in infarcted rats treated with metoprolol compared with infarcted untreated rats (p = 0.03). There were, however, no significant differences in the expansion index, thinning ratio, or left ventricular volume between the two infarcted groups. Thus metoprolol therapy begun in the immediate postinfarction period promotes an increase in left ventricular weight and reduces operative volume stiffness but has no significant effect on indexes of early infarct expansion.

Animals↗
PubMed1994

Effects of treatment on outcome in mildly symptomatic patients with ischemia during daily life. The Atenolol Silent Ischemia Study (ASIST)

BACKGROUND: Detection of asymptomatic ischemia in patients with coronary artery disease has been associated with increased risk for adverse outcome, but treatment of patients with asymptomatic ischemia remains controversial. Accordingly, the purpose of this study was to determine if treatment reduces adverse outcome in patients with daily life ischemia. METHODS AND RESULTS: A multicenter, randomized, double-blind, placebo-controlled study of asymptomatic or minimally symptomatic outpatients with daily life silent ischemia due to coronary artery disease was conducted. The primary outcome measure was event-free survival at 1 year by Kaplan-Meier analysis. Events were death, resuscitated ventricular tachycardia/fibrillation, myocardial infarction, hospitalization for unstable angina, aggravation of angina, or revascularization. The secondary outcome was ischemia during ambulatory ECG monitoring at 4 weeks. Three hundred six outpatients with mild or no angina (Canadian Cardiovascular Society class I or II), abnormal exercise tests, and ischemia on ambulatory monitoring were randomized to receive either atenolol (100 mg/d) or placebo. After 4 weeks of treatment, the number (mean +/- SD, 3.6 +/- 4.2 versus 1.7 +/- 4.6 episodes, P < .001) and average duration (30 +/- 3.3 versus 16.4 +/- 6.7 minutes, P < .001) of ischemic episodes per 48 hours of ambulatory monitoring decreased in atenolol- compared with placebo-assigned patients (4.4 +/- 4.6 to 3.1 +/- 6.0 episodes and 36.6 +/- 4.1 to 30 +/- 5.5 minutes). Event-free survival improved in atenolol-treated patients (P < .0066), who had an increased time to onset of first adverse event (120 versus 79 days) and fewer total first events compared with placebo (relative risk, 0.44; 95% confidence intervals, 0.26 to 0.75; P = .001). There was a nonsignificant trend for fewer serious events (death, resuscitation from ventricular tachycardia/fibrillation, nonfatal myocardial infarction, or hospitalization for unstable angina) in atenolol-treated patients (relative risk, 0.55; 95% confidence intervals, 0.22 to 1.33; P = .175). The most powerful univariate and multivariate correlate of event-free survival was absence of ischemia on ambulatory monitoring at 4 weeks. Side effects were mild and generally similar comparing atenolol- and placebo-treated patients, although bradycardia was more frequent with atenolol. CONCLUSIONS: Atenolol treatment reduced daily life ischemia and was associated with reduced risk for adverse outcome in asymptomatic and mildly symptomatic patients compared with placebo.

Activities of Daily Living↗
PubMed1993

Initial clinical presentation of cardiac disease in asymptomatic men with silent myocardial ischemia and angiographically documented coronary artery disease (the Oslo Ischemia Study).

Data concerning the natural history of asymptomatic coronary artery disease (CAD) has been limited to epidemiologic rather than angiographic studies, thus leading to uncertainty as to whether warning symptoms and signs will identify subjects with silent myocardial ischemia before morbid events. To address this issue, 50 apparently healthy men with angiographically proven CAD and asymptomatic exercise-induced ST depression have been followed prospectively for 15 years in the Oslo Ischemia Study. Fourteen men died. The initial presenting clinical event in these 14 men was chest pain in 4 (30%)--but in only 1 case was it recognized as typical angina--silent myocardial infarction in 5 (35%) and sudden death in 5 (35%). Thirty-six men survived, with 19 developing symptoms. Overall, chest pain was the first clinical event in 22 of the total of 33 men with symptoms (66%), whereas myocardial infarction occurred in 6 (18%) and sudden death in 5 (16%). Although chest pain occurred in 22 men, it was clinically diagnosed as typical angina pectoris in only 6. These observations suggest that there is an absence of clear-cut ischemic symptoms in many asymptomatic patients before morbid events.

Adult↗
PubMed1993

The effects of chronic oral milrinone therapy on early postinfarction left ventricular remodeling.

Left ventricular remodeling following acute transmural myocardial infarction may result in early left ventricular enlargement. To characterize the effects of milrinone on components of early left ventricular dilation, rats (n = 120) underwent left coronary artery ligation or sham surgery. In the immediate postoperative period, rats received either no treatment or milrinone (3.17 +/- 0.08 mg/kg/day) dissolved in drinking water for 20 days. Twenty-one days after the initial surgery, hemodynamic measurements were made. The rats were then put to death and the hearts arrested in diastole were excised and fixed at a constant pressure for morphometric analysis. To examine the effects of milrinone on the relative contribution of infarcted and noninfarcted segments to early left ventricular dilation after acute myocardial infarction, a subgroup of infarcted rats chosen randomly was put to death 3 days after the initial surgery for morphometric analysis. Compared with infarcted untreated rats, infarcted milrinone-treated rats had a lower left ventricular volume (1.41 +/- 0.07 ml/kg vs 2.16 +/- 0.19 ml/kg, p < 0.001), lower left ventricular wall stress (0.64 +/- 0.03 vs 0.91 +/- 0.06, p < 0.001), and a lower expansion index (1.61 +/- 0.12 vs 2.61 +/- 0.22, p < 0.001). Morphometric analysis revealed that the noninfarcted segment length did not differ between the two infarcted groups either 3 days or 21 days after left coronary artery ligation. Infarct segment length also did not differ between the two infarcted groups at 3 days, but at 21 days infarct segment was shorter in the milrinone-treated group compared with the untreated group (p < 0.03).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗