Bryan G. Schwartz

Cardiovascular Effects of Cocaine

The use of cocaine has evolved from chewing the leaves of the Erythroxylon coca bush thousands of years ago, to purification of cocaine hydrochloride over 100 years ago and its use in tonics and elixirs (at one time in popular cola drinks), to insufflating and injecting the fine, white, water-soluble, powder form, to a smokable freebase form called “crack,” which became popular in the 1980s.1 In 2007, 2.1 million Americans had recent cocaine use; 1.6 million met criteria for cocaine dependence or abuse.1 Cocaine accounted for 31% of all visits to the emergency department related to drug misuse or abuse.1 From 1971 to 1987, the incidence of deaths caused by cocaine overdose increased 20-fold in Dade County, Florida.2 In a consecutive series of 233 emergency visits by cocaine-using patients, 56% presented with cardiovascular complaints, including 40% with chest pain.3 A minority of these patients have acute myocardial infarction (MI) (≈6%),4,–,7 and overall mortality is low (<1%).3,–,5,8,–,10 However, cocaine is associated with a number of cardiovascular diseases, including MI, heart failure, cardiomyopathies, arrhythmias, aortic dissection, and endocarditis. Identifying patients with acute disease is challenging. This review describes the relationship between cocaine and various cardiovascular diseases, as well as appropriate diagnostic evaluation and therapies. ### Molecular Cocaine stimulates the sympathetic nervous system by inhibiting catecholamine reuptake at sympathetic nerve terminals,11,12 stimulating central sympathetic outflow,11 and increasing the sensitivity of adrenergic nerve endings to norepinephrine (Figure 1).12 Cocaine also acts like a class I antiarrhythmic agent (local anesthetic) by blocking sodium and potassium channels, which depresses cardiovascular parameters.13 Of these 2 primary, opposing actions, enhanced sympathetic activity predominates at low cocaine doses, whereas the local anesthetic actions …

Cardiac Uses of Phosphodiesterase-5 Inhibitors

Phosphodiesterase-5 inhibitors (PDE5Is) improve erectile function by enhancing nitric oxide availability in the penis and its supplying vasculature, resulting in vasodilation and increased blood flow. PDE5Is might benefit cardiovascular diseases because phosphodiesterase-5 is also located elsewhere in the body, including the pulmonary and systemic vasculature and in hypertrophied myocardium. PDE5Is are approved for pulmonary arterial hypertension, given that they improved several hemodynamic and clinical parameters in large randomized trials. Initial evidence suggests that PDE5Is benefit patients with congestive heart failure and secondary pulmonary hypertension. PDE5Is seem to improve hemodynamic and clinical parameters in patients with high-altitude pulmonary edema (HAPE) and high-altitude pulmonary hypertension. In climbers with prior episodes of HAPE, PDE5Is prevented HAPE in 2 small randomized trials. In small randomized trials of PDE5Is, patients with Raynauds phenomenon demonstrated improved blood flow, fewer symptoms and frequency of attacks, and resolution of digital ulcers. In addition to enhancing vasodilation, PDE5Is seem to protect the myocardium through complex pathways that involve nitric oxide, cyclic guanosine monophosphate, protein kinase G, extracellular-signal-regulated kinase, B-cell lymphoma protein-2, and Rho kinase inhibition. In animal models of acute myocardial infarction, PDE5Is consistently reduced infarct size indicating cardioprotection and PDE5Is also promote reverse remodeling and reduce myocardial apoptosis, fibrosis, and hypertrophy. PDE5Is might also benefit patients with treatment-resistant hypertension, preeclampsia, or peripheral arterial disease. This review presents the pathophysiology and trial data with regard to the use of PDE5Is for cardiac diseases.

Drug Interactions With Phosphodiesterase-5 Inhibitors Used for the Treatment of Erectile Dysfunction or Pulmonary Hypertension

Sildenafil and tadalafil were the 32nd and 74th, respectively, most popular prescription drugs dispensed in the United States in 2006. Erectile dysfunction (ED) currently affects >30 million men in the United States and >150 million men worldwide and will become more prevalent as the population ages.1 Phosphodiesterase-5 (PDE5) inhibitors (PDE5Is) (sildenafil [Viagra],2 vardenafil [Levitra],3 and tadalafil [Cialis]4) are first-line therapy for ED. Use of PDE5Is will increase because sildenafil (Revatio)5 and tadalafil (Adcirca)6 are now prescribed as first-line therapy for many patients with pulmonary hypertension (PHT).5–8 Several pooled analyses comprising dozens of trials and thousands of patients, including patients with coronary artery disease and on antihypertensive medications, reported that PDE5Is did not significantly affect the incidence of adverse cardiovascular events.9–12 However, PDE5 is distributed in many tissues, including platelets, veins, and arterial smooth muscle (pulmonary, coronary, and systemic arteries).13 Thus, PDE5Is affect the cardiovascular system, mostly via vasodilation, and often cause small decreases in blood pressure (BP). When PDE5Is are coadministered with nitrates or α-blockers, pronounced systemic vasodilation and severe hypotension are possible. Many patients with ED are elderly and have the same risk factors as patients with coronary artery disease, so these drug combinations are commonly considered or encountered in clinical practice.1 This article covers the important PDE5I drug interactions, including antihypertensive agents, nitrates, α-blockers, PHT agents, cytochrome P450 inhibitors, and other miscellaneous drugs. Sildenafil is metabolized mainly by the cytochrome P450 3A4 pathway (79%) and to a lesser extent by 2C9 (20%).14,15 Vardenafil is metabolized in a similar manner, mainly by 3A4 with a smaller contribution by 2C9.15 Tadalafil is metabolized almost solely by 3A4.15 Therefore, drugs that inhibit the 3A4 pathway decrease the metabolism and increase the plasma concentrations of PDE5Is (Table 1). Area …

Emotional stressors trigger cardiovascular events

Aims:  To describe the relation between emotional stress and cardiovascular events, and review the literature on the cardiovascular effects of emotional stress, in order to describe the relation, the underlying pathophysiology, and potential therapeutic implications.

Therapeutic hypothermia for acute myocardial infarction and cardiac arrest.

This report focuses on cardioprotection and describes the advantages and disadvantages of various methods of inducing therapeutic hypothermia (TH) with regard to neuroprotection and cardioprotection for patients with cardiac arrest and ST-segment elevation myocardial infarction (STEMI). TH is recommended in cardiac arrest guidelines. For patients resuscitated after out-of-hospital cardiac arrest, improvements in survival and neurologic outcomes were observed with relatively slow induction of TH. More rapid induction of TH in patients with cardiac arrest might have a mild to modest incremental impact on neurologic outcomes. TH drastically reduces infarct size in animal models, but achievement of target temperature before reperfusion is essential. Rapid initiation of TH in patients with STEMI is challenging but attainable, and marked infarct size reductions are possible. To induce TH, a variety of devices have recently been developed that require additional study. Of particular interest is transcoronary induction of TH using a catheter or wire lumen, which enables hypothermic reperfusion in the absence of total-body hypothermia. At present, the main methods of inducing and maintaining TH are surface cooling, endovascular heat-exchange catheters, and intravenous infusion of cold fluids. Surface cooling or endovascular catheters may be sufficient for induction of TH in patients resuscitated after out-of-hospital cardiac arrest. For patients with STEMI, intravenous infusion of cold fluids achieves target temperature very rapidly but might worsen left ventricular function. More widespread use of TH would improve survival and quality of life for patients with out-of-hospital cardiac arrest; larger studies with more rapid induction of TH are needed in the STEMI population.

Phosphodiesterase Type 5 Inhibitors Improve Endothelial Function and May Benefit Cardiovascular Conditions

The effects of phosphodiesterase type 5 inhibitors on vasodilation mediated via nitric oxide-cyclic guanosine monophosphate are well described. Less is known about other mechanisms through which phosphodiesterase type 5 inhibitors benefit endothelial function, including normalization of serum biomarkers, increased levels of endothelial progenitor cells, ischemia-reperfusion protection mechanisms, and other actions specific to patients with diabetes. These various mechanisms are reviewed. Their impact on several cardiovascular diseases, including erectile dysfunction, pulmonary hypertension, heart failure, high-altitude pulmonary edema, Raynauds phenomenon, coronary artery disease, diabetes, and atherosclerosis, is presented.

Cardiovascular Implications of Erectile Dysfunction

Sexual problems might mean you have a broken heart, literally. The most common sexual problem in men is erectile dysfunction (ED). ED affects up to 30 million men in the United States. Surprisingly, ED might be a sign of heart problems. It is important to discuss sexual health with your doctor. Not only can your doctor prescribe medications to improve sexual function, but together you may be able to prevent a major heart problem like a heart attack. This article outlines the steps that you should take if you think you have ED. Erectile dysfunction means that a man is not able to have sex because he cannot get or keep an erection. Erectile dysfunction affects >30% of men between 40 and 70 years of age. There are several different causes of ED, including depression, low testosterone, nerve problems, and some medications, but the most common cause is a problem with the blood vessels called atherosclerosis. With atherosclerosis, the blood vessels are not able to dilate properly, which is called endothelial dysfunction (see the Figure). Cholesterol builds up in the blood vessel walls and forms plaques, which make the vessels narrow and slow down blood flow. When a plaque becomes very advanced, it can completely stop blood from passing through, which is what happens in a heart attack. Atherosclerosis affects not only the blood vessels supplying the heart (coronary arteries), but also blood vessels throughout the entire body. Atherosclerosis causes angina (chest pain that is often exertional), heart attacks, strokes, …

Relation of Total and Cardiovascular Death Rates to Climate System, Temperature, Barometric Pressure, and Respiratory Infection.

A distinct seasonal pattern in total and cardiovascular death rates has been reported. The factors contributing to this pattern have not been fully explored. Seven locations (average total population 71,354,000) were selected where data were available including relatively warm, cold, and moderate temperatures. Over the period 2004 to 2009, there were 2,526,123 all-cause deaths, 838,264 circulatory deaths, 255,273 coronary heart disease deaths, and 135,801 ST-elevation myocardial infarction (STEMI) deaths. We used time series and multivariate regression modeling to explore the association between death rates and climatic factors (temperature, dew point, precipitation, barometric pressure), influenza levels, air pollution levels, hours of daylight, and day of week. Average seasonal patterns for all-cause and cardiovascular deaths were very similar across the 7 locations despite differences in climate. After adjusting for multiple covariates and potential confounders, there was a 0.49% increase in all-cause death rate for every 1°C decrease. In general, all-cause, circulatory, coronary heart disease and STEMI death rates increased linearly with decreasing temperatures. The temperature effect varied by location, including temperatures linear slope, cubic fit, positional shift on the temperature axis, and the presence of circulatory death increases in locally hot temperatures. The variable effect of temperature by location suggests that people acclimatize to local temperature cycles. All-cause and circulatory death rates also demonstrated sizable associations with influenza levels, dew point temperature, and barometric pressure. A greater understanding of how climate, temperature, and barometric pressure influence cardiovascular responses would enhance our understanding of circulatory and STEMI deaths.

Metoclopramide and Digoxin Cause 22 Episodes of Bradyarrhythmias

ASE REPORT 56-year-old white man with hypertension suffered a 62% otal body surface area burn (day 0). On day 4 the patient eveloped atrial fibrillation with a rapid ventricular reponse, treated acutely with amiodarone and digoxin. The atient then demonstrated paroxysmal atrial fibrillation, reated with digoxin. The patient spent 6 months in the ntensive care unit and underwent 11 operations to treat his urns. On day 20, the patient underwent pyloroplasty for a leeding ulcer, then developed postoperative ileus. Metolopramide 20 mg was administered intravenously every 6 ours and continued indefinitely. Beginning on day 54, the patient experienced 7 episodes f bradycardia and 15 episodes of asystole over 48 hours. ome required atropine, while others resolved spontaneusly. Some converted initially to a junctional rhythm; all ltimately reverted to sinus tachycardia. Serial electrocariograms were normal. A noncardiac cause of asystole was suspected. After xcluding other possibilities, 2 medications were identified s probable etiologies: digoxin and metoclopramide; both ere discontinued. Several hours later the bradyarrhythmias topped. Afterward, the patient continued to tolerate tube feedings nd, eventually, a regular diet. Paroxysmal atrial fibrillation as treated with amiodarone, then diltiazem. On day 170, he patient was transferred to an acute rehabilitation facility.

When and why do heart attacks occur? Cardiovascular triggers and their potential role.

Abstract Coronary heart disease affects 7.6% of the population in the United States, where > 900 000 myocardial infarctions (MIs) occur annually. Approximately half of all MIs have an identifiable clinical trigger. Myocardial ischemia, MI, sudden cardiac death, and thrombotic stroke each occur with circadian variation and peak after waking in the morning. In addition, physical exertion and mental stress are common precipitants of MI. Waking in the morning, physical exertion, and mental stress influence a number of physiologic parameters, including blood pressure, heart rate, plasma epinephrine levels, coronary blood flow, platelet aggregability, and endothelial function. Upregulation of sympathetic output and catecholamines increase myocardial oxygen demand and can decrease myocardial oxygen supply and promote thrombosis. Ischemia ensues when myocardial oxygen demand exceeds supply. Increases in blood pressure and ventricular contractility increase intravascular shear stress and may cause vulnerable atherosclerotic plaques to rupture, forming a nidus for thrombosis that can precipitate MI. Numerous clinical triggers of MI have been identified, including blizzards, the Christmas and New Years holidays, experiencing an earthquake, the threat of violence, job strain, Mondays for the working population, sexual activity, overeating, smoking cigarettes, smoking marijuana, using cocaine, and particulate air pollution. Avoiding clinical triggers or participating in therapies that prevent clinical triggers from precipitating cardiac events could potentially postpone clinical events by several years and improve cardiovascular morbidity and mortality. Direct or indirect evidence suggests that the risk of triggered MIs is reduced with β-blockers, aspirin, statins, stress management, and transcendental meditation.