Journal of Cardiovascular Pharmacology and Therapeutics

With longer life expectancy, as well as better survival rates after myocardial infarction, the population of elderly patients with congestive heart failure steadily increases. Large, randomized, placebo-controlled studies have shown significant beneficial effects for several classes of drugs (angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, β-blockers, aldosterone antagonists) in patients with congestive heart failure. In most of these studies, however, elderly patients were either excluded or represented only a minority of the study population. Therefore, the treatment benefit for the large population of patients aged 65 and older is still not very well documented. In this paper, we critically review the current literature with regard to outcome of heart failure therapy in this particular subpopulation.

Recently, cyclooxygenase-2 (COX-2) inhibitors (coxibs), a class of drugs intended to be painkillers, have created unprecedented controversy because of their cardiovascular risk profile. The controversy has affected the patients, health-care providers, the Food and Drug Administration, and the manufacturers of these agents alike. We summarize the mechanisms of actions of this class of agents, their cardiovascular risk as evident in multiple trials, the basis of their adverse risk profile, and our views on this issue.

There is strong evidence that excess dietary salt (NaCl) is a major factor contributing to the development of hypertension. Salt-sensitive humans and rats develop hypertension even on a normal-salt diet. Salt sensitivity is associated with glucose intolerance and insulin resistance in both humans and animal models, including Dahl salt-sensitive (DSS) rats. In insulin resistance, impaired glucose metabolism leads to elevated endogenous aldehydes that bind sulfhydryl groups of membrane proteins, altering calcium channels, and increasing cytosolic free calcium ([Ca²⁺] _i ) and blood pressure. Vitamin E lowers tissue aldehyde conjugates, cytosolic [Ca²⁺] _i , and blood pressure in spontaneously hypertensive rats and fructose-induced hypertensive Wistar Kyoto rats, models of insulin resistance. This study investigated the effect of a normal-salt diet on tissue aldehyde conjugates, cytosolic [Ca²⁺] _i , and blood pressure in DSS rats and the effect of vitamin E supplementation on blood pressure and associated biochemical changes in these animals. Seven-week-old DSS rats were divided into 3 groups of 6 animals each and treated for 6 weeks with diets as follows: low-salt (0.4% NaCl); normal-salt (0.7% NaCl) and normal salt (0.7% NaCl) plus vitamin E (34 mg/kg feed). At completion, animals in the normal-salt group had significantly elevated systolic blood pressure, cytosolic [Ca²⁺] _i , and tissue aldehyde conjugates compared with the low-salt group. They also showed smooth muscle cell hyperplasia in small arteries and arterioles of the kidney. Dietary vitamin E supplementation significantly attenuated the increase in systolic blood pressure and associated biochemical and histopathologic changes.

Introduction: Earlier studies have implicated the adverse effects of β- and α₁-adrenergic receptors during cardiopulmonary resuscitation (CPR). Because carvedilol is both a nonselective β- and α₁-selective adrenergic receptor-blocking agent, we hypothesized that pre-treatment with carvedilol would convert the actions of epinephrine to that of a selective a2-agonist.

Methods: Ventricular fibrillation (VF) was induced in Sprague-Dawley rats weighing approximately 500 g. Animals were randomized to 4 groups of 5 animals each: (1) placebo pretreatment and epinephrine treatment, (2) carvedilol pretreatment and placebo treatment, (3) carvedilol pretreatment and epinephrine treatment, and (4) placebo pretreatment and placebo treatment. Carvedilol (50 µg/kg) was injected as a bolus into the right atrium 15 minutes before VF was induced. VF was untreated for 8 minutes, after which CPR (chest compression and mechanical ventilation) was begun. Epinephrine (30 µg/kg) was injected into the right atrium 2 minutes after the start of CPR. Electrical defibrillation was attempted after 14 minutes of VF.

Results: All but 2 animals were successfully resuscitated. Approximately equivalent increases in coronary perfusion pressure from 23 ± 1 mm Hg to 30 ± 3 mm Hg were observed after the injection of epinephrine independently of carvedilol pretreatment. Carvedilol pretreatment followed by epinephrine treatment reduced early postresuscitation ventricular ectopy (116 ± 147 vs 834 ± 380, P < .01) and minimized increases in arterial blood lactate at 5 minutes after resuscitation (10.9 ± 2.1 mmol/L vs 17.4 ± 3.5 mmol/L, P < .01). The postresuscitation cardiac index measured 4 hours later was increased (307 ± 43 mL • min^-1• kg^-1 vs 210 ±6 mL • min^-1• kg^-1, P <.05). Left ventricular diastolic pressures were decreased (6 ± 1 vs 14 ± 1 mm Hg, P < .05). Animals pretreated with carvedilol survived longer (71 ± 1 vs 45 ± 22 hours, P < .05) and with less postresuscitation neurologic deficit.

Conclusion: After β- and α₁-adrenergic blockade with carvedilol before inducing cardiac arrest, epinephrine administered during CPR yielded better postresuscitation myocardial and neurologic functions and significantly increased postresuscitation survival.

Background: Myocardial stunning is a lingering contractile dysfunction that occurs after brief ischemia, even in the absence of necrosis. Recent studies have shown that acetaminophen may have some benefit on the return of left ventricular function after brief global ischemia in an in vitro model. This study was conducted to determine whether treatment with acetaminophen results in enhanced myocardial tolerance to transient ischemia-reperfusion by improving left ventricular function and decreasing stunning in an in vivo model.

Methods: Anesthetized, open-chest rabbits were randomized to receive acetaminophen (37 mg/kg, n = 13) or saline (n = 11) 15 minutes before a series of transient coronary artery occlusions followed by reperfusion (three 10-minute periods of ischemia with 5 minutes reperfusion between). Hemodynamics and maximal and minimal values of developed pressure velocity (dP/dt) were measured at baseline, during ischemia, and throughout 2 hours of reperfusion. To assess myocardial stunning, echocardiography was used to determine regional systolic wall thickening fractions and global indices of function such as LV cavity dimensions and ejection fraction.

Results: Hemodynamic variables, including left ventricular systolic pressure and positive and negative dP/dt, were similar in both groups throughout the study. Left ventricular enddiastolic pressure was significantly lower in the acetaminophen group during occlusion and early reperfusion. The repeated short periods of ischemia in the free wall of the heart caused myocardial stunning in both groups. During ischemia, contractile function in the free wall was severely reduced, and although it improved during reperfusion, dysfunction persisted in the postischemic free wall after 2 hours of reflow, recovering to less than 52% of preischemic values (P < .01). The degree of dysfunction was similar in both groups. During ischemia, the end-diastolic left ventricular cavity area increased from 1.14 ± 0.05 cm² at baseline to 1.33 ±0.08 cm² (P < .05) in controls, but had recovered after 2 hours of reflow. The end-diastolic area in acetaminophen-treated hearts increased from 1.13 ± 0.08 cm²at baseline to 1.35 ± 0.08 cm² during ischemia and also recovered 2 hours later. No significant differences in LV cavity areas were noted between the groups. Acetaminophen had no effect on changes in ejection fraction, which decreased similarly in both groups during ischemia to approximately 75% of baseline values. Although ejection fraction improved, it remained depressed at the end of reflow in both groups.

Conclusion: Data from this study show that in a rabbit model of myocardial stunning, acetaminophen has a neutral effect on hemodynamics, recovery of fractional thickening, and on indices of global recovery such as left ventricular cavity dimensions or ejection fraction. Thus in the setting of experimental myocardial stunning, treatment with acetaminophen was safe but not cardioprotective.

In a patient with persistently elevated troponin levels but normal ischemic work-up, a diagnostic dilemma can ensue. This is the case of a 65-year-old woman whose only cardiac risk factor was age. She presented repeatedly with chest pain, elevated troponins, and consistently elevated eosinophil levels until the fourth admission when she presented with multi-organ abnormalities including asthma and vasculitis that led to the diagnosis of Churg-Strauss syndrome (CSS). Initiation of corticosteroids immediately resolved all of her presenting symptoms; troponin and eosinophil levels quickly normalized. Eosinophilia from CSS can lead to multi-organ damage including the heart. Therefore, one must consider CSS in the differential of eosinophilia as early detection and treatment may be critical in decreasing morbidity and mortality.

Myocardial calcification is a manifestation of either metastatic or dystrophic calcium deposition in the myocardium. Dystrophic calcification of the myocardium is most commonly seen in long-term survivors of substantial myocardial infarctions. Current literature has reported only 3 cases of myocardial calcification with normal coronary arteries. We present a case of an 80-year-old woman with multiple admissions over a 5-year period for congestive heart failure. She was found to have a normal left ventricular ejection fraction and normal coronary arteries on left heart catheterization. A high resolution computed tomography (CT) study of the chest revealed extensive left ventricular myocardial calcifications, which were not present 4 years earlier on CT. The patient’s history and clinical presentation revealed no etiologic factors for her calcified myocardium.