The atherosclerotic plaque.

Atherosclerosis is the most frequent cause of ischemic heart disease and cerebrovascular disorders. The condition is the leading cause of death in Western societies. At the core of this condition is the atherosclerotic plaque. It is within the structure of this lesion that multiple biochemical and cellular processes interact influencing its vulnerability to rupture and as a result acute ischemic events. This article will discuss the pathophysiology behind the atherosclerotic plaque, particularly those elements that lead to its instability and the medical tools currently available to counteract it.

Coronary artery abnormalities in Puerto Rico

A retrospective study was done to determine the frequency of coronary artery anomalies in terms of their origin, course, and structure. The clinical history, catheterization data and surgical reports of patients undergoing coronary angiography at the Cardiovascular Center of Puerto Rico and the Caribbean, from 1999 to 2004, were analyzed. Thirty-eight patients were identified with a coronary artery anomaly in this population. These anomalies were classified according to their clinical consequences and the need for surgical intervention.

Heart transplantation in females: the experience in Puerto Rico

BACKGROUND: Heart transplantation is the procedure of choice for a selected group of patients with end stage heart disease. Gender related differences have been observed in the heart transplant field: less women than men are recipients of heart transplants, more risk of rejection in female recipients, and a perception toward reduced survival in women. We report our experience of heart transplantation in females in Puerto Rico. METHODS: We studied the data bank of 69 heart transplant recipients in the Puerto Rico Heart Transplant Program from June 1999 to June 2005. Gender related differences in the number of recipients: males or females, incidence of rejection, survival, and other outcomes were analyzed. RESULTS: 69 patients received an orthotopic heart transplant from June 1999 to June 2005, in a single center in Puerto Rico. The mean age of the patients was 47 (11-62) years. Fifty patients (72%) were men, and 19 patients (28%), were women. Survival in the female group at 3 months, 1, 2, 3, 4, and 5 years was 100%, 100%, 100%, 100%, 90%, and 90% respectively. The survival in the male group at 3 months, 1, 2, 3, 4 and 5 years was 97%, 97%, 97%, 94%, 86 and 79% respectively. There was an early, higher incidence of rejection in women during the first three months post transplant; 1.5 vs. 0.75, (P=0.04) episodes per patient in the female, and male group respectively. After the third month post transplant there was no significant difference in rejection incidence. The incidence of infectious episodes was significantly more frequent in female than in male recipients, 2.8 vs. 1 (P=0.02) per patient respectively. CONCLUSIONS: There were more male than female heart transplant recipients at a ratio of 3:1, without a significant gender difference in survival. The risk of rejection was higher in females in the early period post transplantation, but thereafter this risk showed no signinificant statistical difference. The incidence of infection was more frequent in female...

[Total plasma homocysteine concentrations in Puerto Rican patients with ischemic heart disease]. / Concentraciones totales de homocisteína plasmática en pacientes puertorriqueños con cardiopatía isquémica.

INTRODUCTION AND OBJECTIVES: In Puerto Rico, it has been established that although coronary disease is the leading cause of death, the population has a lower incidence of coronary disease than in the continental United States. In addition, the severity of the disease is less aggressive in terms of a lower incidence of ventricular tachycardia and sudden death. One factor that could contribute to the lower incidence of coronary disease in Puerto Rico is that our population might have lower total plasma homocysteine concentrations (tHcys) than in the continental United States. Our main objective was to measure tHCys in the Puerto Rican population with atherosclerotic cardiovascular disease (ACD). METHODS: We randomly measured tHcys concentrations in seventy Puerto Rican patients who were hospitalized at the Cardiovascular Center of Puerto Rico and the Caribbean (UPR Division). RESULTS: The mean tHCys concentration in these patients is similar to those reported for the Framingham study when adjusted by age (11.2 vs. 11.8 micromol/l). In the Puerto Rican population, males had a higher tHcys concentration than females (11.7 vs 9.5 micromol/l, p = 0.07). In addition, we did not see an increase of tHcys concentrations in diabetic patients when compared with non-diabetics (10.1 vs. 11.2 micromol/l, p = 0.74). We did not see a direct correlation between tHcys concentrations and heart condition as measured by coronary angiography (normal = 11.1 micromol/l, light = 10.5 micromol/l, moderate = 10.9 micromol/l, severe = 10.5 micromol/l; Kruskal-Wallis = 0.45) either. CONCLUSION: These results suggest that tHcys concentration is not a good predictor of the seriousness of ACD in the Puerto Rican patient population.

Relationship between NO synthesis, arginine transport, and intracellular arginine levels in vascular smooth muscle cells.

The present study was designed to evaluate the relevance of arginine transport in nitric oxide (NO) synthesis in vascular smooth muscle cells. For this purpose, NO synthesis and arginine transport (system B0,+ and y+) were evaluated in cells treated with IL-1beta or angiotensin II (Ang II). In addition, the effects of 5 mM lysine and glutamine, competitive inhibitors of systems y+ and B0,+ respectively, were examined. L-arginine transport was estimated with 3H-labelled arginine and NO was determined with the Griess reagent. These studies were done in control conditions, arginine-starved cells, and in cells incubated in media containing 10 mM arginine. Our data indicate that induction of NO biosynthesis by IL-1beta depends on external arginine when cells are arginine-depleted for 24 hours. The concentration of arginine producing half maximal activation of NO synthesis in arginine-depleted cells ([arginine]i < 10 microM) was 41.1 +/- 18 microM. By contrast, in normal culture conditions, NO synthesis occurred independently of arginine transport. Neither 5 mM lysine or glutamine which abolished arginine transport through systems y+ and B0,+, respectively, reduced nitrite release in cells incubated in normal media. This suggests that the relevance of arginine uptake to NO synthesis depends on the status of intracellular arginine pools. Intracellular arginine concentrations were not affected by the stimulation of NO production using IL-1beta or its inhibition using Ang II, but were markedly reduced by arginine starvation for 48h. Aspartate levels were also reduced by arginine-depletion, but were not affected in cells incubated with 10 mM arginine. By contrast, glutamate levels were reduced in arginine-starved cells and were increased in cells incubated in arginine-supplemented medium. Ornithine levels were markedly increased by arginine supplementation. Altogether, these findings indicate that NO synthesis is normally independent of membrane transport. However in arginine-depleted cells, membrane transport is essential for NO synthesis. It is concluded that arginine transport is required for the long-term maintenance of intracellular arginine pools.

Total plasma homocysteine concentrations in Puerto Rican patients with presumptive atherosclerotic coronary disease.

BACKGROUND: In Puerto Rico, it has been established that although coronary heart disease is the leading cause of death, the population has a lower incidence of coronary disease than the continental United States. In addition, the severity of the disease is less aggressive in terms of a lower incidence of ventricular tachycardia and sudden death. A factor in the lower incidence of coronary disease in Puerto Rico could be a lower total plasma homocysteine concentration (tHcys) in our population. METHODS: We randomly measured tHcys concentrations in seventy-two Hispanic patients who were hospitalized for coronary angiography at the Cardiovascular Center of Puerto Rico and the Caribbean (UPR Division). RESULTS: The mean tHCys concentration in our patient population is similar than that reported for the Framingham study when adjusted by age (11.2 mumol/L vs. 11.8 mumol/L). In the Puerto Rican population, males had a higher tHcys concentration than females but this difference was not statistically significant (10.9 mumol/L vs. 9.4 mumol/L, p = 0.09). In addition, we did not see an increase of tHcys concentrations in diabetic patients when compared with nondiabetics (10.1 mumol/L vs. 10.3 mumol/L, p = 0.73). Neither we saw a direct correlation between tHcys concentrations and atherosclerosis as measured by coronary angiography (normal = 10.9 mumol/L, mild = 8.6 mumol/L, moderate = 10.9 mumol/L, severe = 10.5 mumol/L; ANOVA = 0.29). CONCLUSIONS: These results suggest that tHcys concentration is not a good predictor of atherosclerotic coronary disease in our patient population.

Eleven years experience with the Medtronic Hall Valve

We are reporting our experience of eleven years with the Medtronic Hall Valve. Four hundred twenty two patients received the valve with a mortality of 7.9 por cento

Eleven years experience with the Medtronic Hall Valve.

We are reporting our experience of eleven years with the Medtronic Hall Valve. Four hundred twenty two patients received the valve with a mortality of 7.9%.

Altered vascular function in early stages of heart failure in hamsters.

BACKGROUND: Congestive heart failure is a clinical condition associated with alterations in the normal balance of neurohumoral agents and factors acting on the vascular wall. The etiology of this condition, however, remains largely undefined. To help elucidate the pathophysiology of this disease, vascular function and angiotensin-converting enzyme activity were evaluated in 2-month-old Syrian cardiomyopathic hamsters (SCHs) that had not yet developed heart failure. Age-matched normal hamsters were used as control hamsters. METHODS AND RESULTS: Vascular function studies included determinations of contractile responses of aortic rings to 0.1 microM angiotensin II and 0.1 microM norepinephrine. In addition, endothelial function was evaluated by the vasorelaxant action of acetylcholine on norepinephrine-precontracted aortic rings. The results indicate that the pressor effect of angiotensin II (0.1 microM) was 35% greater in aortic rings from SCRs than that observed in control animals. This effect is specific for angiotensin II because the contraction induced by NE (0.1 microM) was similar in both of these strains. Angiotensin-converting enzyme activity was three-fold higher in aorta homogenates from SCHs but normal in plasma and heart tissue when compared with control hamsters. Aortic ring preparations from SCHs also exhibited endothelial dysfunction because the maximal relaxation elicited by 10 microM acetylcholine was reduced 53%. Concentration-response curves with acetylcholine yielded EC50 values that were threefold lower in SCHs (97.2 +/- 0.1 nM) than in control animals (286 +/- 7 nM). Indomethacin (1 microM) increased the vasorelaxant effect of acetylcholine 28% in SCHs and shifted to the left the concentration-response curve of this agonist, suggesting an increased relaxation with the cyclooxygenase inhibitor. No effect of indomethacin on acetylcholine-induced relaxation was observed in control animals. Sodium nitroprusside induced similar relaxations in both control animals and SCHs, suggesting that the vascular smooth muscle response is normal in SCR. CONCLUSIONS: Altogether these results point to a state of enhanced vascular contractility in young SCHs that could predispose these animals to develop heart failure, the enhanced vascular contractility could result from increased activity of the local renin-angiotensin system, augmented vascular response to angiotensin II, reduced nitric oxide synthesis, and enhanced production of prostaglandins.

Simvastatin releases Ca2+ from a thapsigargin-sensitive pool and inhibits InsP3-dependent Ca2+ mobilization in vascular smooth muscle cells.

Simvastatin (SV), an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase activity inhibits migration and proliferation of vascular smooth muscle cells (SMC). To investigate whether these effects of SV are related to inhibition of cell calcium mobilization, cultured SMC obtained from rat aorta were loaded with Fura-2 to determine the basal cytosolic free calcium levels ([Ca2+]i) and the agonist-stimulated Ca2+ mobilization. SV (20 mu M) transiently increased cytosolic free calcium, an effect that depends mainly on intracellular calcium release (68%). This effect of SV was markedly reduced (75%) by thapsigargin, an inhibitor of the Ca2+ ATPase of inositol 1,4,5-triphosphate (InsP3)-sensitive calcium pools. Incubation of cells with SV (15 min) inhibited the mobilization of Ca2+ by angiotensin II, platelet-derived growth factor, and vasopressin (IC50 = 5 mu M). SV did not affect inositol trisphosphate (InsP3) levels or modify its generation by angiotensin II (Ang II) and vasopressin. Furthermore, in saponin-permeabilized cells, SV abolished the release of calcium by 2,3-dideoxy-InsP3. SV reduced the effect of thapsigargin on InsP3-sensitive stores by 67%, suggesting that SV depletes these calcium pools. The inhibitory effect of SV on calcium mobilization was prevented by coincubation of cultured cells (24 h) with 1 mM mevalonic acid, the product of HMG-CoA reductase activity. These results support the notion that SV inhibits [corrected] the migration and proliferation of SMC by directly affecting cell Ca2+.

Inhibition of smooth muscle cell calcium mobilization and aortic ring contraction by lactone vastatins.

OBJECTIVE: To determine the effects of vastatins on the contraction of rat aortic rings and to assess their effects on calcium mobilization using cultured smooth muscle cells from rat aorta. METHODS: Aortic rings from Sprague-Dawley rats were mounted on stainless steel wires to determine the generation of tension using force-displacement transducers. The tension (g) developed by angiotensin II (100 nmol/l) was measured under basal conditions and after 45 min incubation with 20 micromol/l simvastatin. The effect of 20 mol/l simvastatin, lovastatin, mevastatin and pravastatin on noradrenaline concentration-response curves and the angiotensin II-induced calcium mobilization was also evaluated. RESULTS: Addition of angiotensin II to aortic rings incubated in Krebs' Ringer bicarbonate medium produced tension generation (0.9 +/- 0.12 g = 100%). Treatment of aortic rings with simvastatin inhibited the angiotensin II-induced contraction 58 +/- 0.06%. To evaluate this effect further, dose-response curves with noradrenaline were measured in the presence and absence of 20 micromol/l simvastatin, lovastatin, mevastatin and pravastatin. The results indicate that simvastatin, lovastatin and mevastatin inhibited the contraction induced by noradrenaline (10 micromol/l) by about 50%. Pravastatin did not inhibit aortic ring contraction. Furthermore, the concentration required for 50% of the maximal contraction (EC50) by noradrenaline (6.2 +/- 0.1 nmol/l) was significantly increased by simvastatin, lovastatin, mevastatin and pravastatin. The inhibition of vascular contraction by vastatins appears to involve inhibition of 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase activity because the inhibitory effect of simvastatin was reduced 50% by 10 mmol/l mevalonic acid. To determine whether the depression of vascular contraction by these agents was correlated with cell calcium changes, the angiotensin II-induced calcium mobilization was determined in Fura-2 loaded cells, before and after treatment with these inhibitors. Simvastatin, lovastatin and mevastatin significantly reduced the angiotensin II-induced calcium mobilization. The concentration that induced 50% inhibition was 3.3 micromol/l for simvastatin, 17.4 micromol/l for mevastatin and 21.7 micromol/l for lovastatin. No effect of pravastatin on calcium mobilization was observed. CONCLUSIONS: These findings suggest that lactone vastatins depress vascular contraction by reducing cytosolic calcium release in vascular smooth muscle cells. These agents also appear to exert competitive and non-competitive type antagonisms on noradrenaline action.

Parallel regulation of arginine transport and nitric oxide synthesis by angiotensin II in vascular smooth muscle cells role of protein kinase C.

Experiments were performed to characterize arginine transport in vascular smooth muscle cells (SMCs) and the effect of angiotensin II (Ang II) on this process. In addition, the role of arginine transport in the cytokineinduced nitric oxide (NO) production was assessed. Arginine transport takes place through Na(+)-independent (≈60%) and Na(+)-dependent pathways (≈40%). The Na(+)-independent arginine uptake appears to be mediated by system y(+) because of its sensitivity to cationic amino acids such as lysine, ornithine and homoarginine. The transport system was relatively insensitive to acidification of the extracellular medium. By contrast, the Na(+)-dependent pathway is consistent with system B(0,+) since it was inhibited by both cationic and neutral amino acids (i.e., glutamine, phenylalanine, and asparagine), and did not accept Li(+) as a Na(+) replacement. Treatment of SMCs with 100nM Ang II significantly inhibited the Na(+)-dependent arginine transport without affecting systems y(+), A, and L. This effect occurred in a dose-dependent manner (IC50 of 8.9 ± 0.9nM) and is mediated by the AT-1 receptor subtype because it was blocked by DUP 753, a non-peptide antagonist of this receptor. The inhibition of system B(0,+) by Ang II is mediated by protein kinase C (PKC) because it was mimicked by phorbol esters (phorbol 12-myristate 13-acetate) and was inhibited by staurosporine. Ang II also inhibited the IL-1ß induced nitrite accumulation by SMCs. This action was also inhibited by staurosporine and reproduced with phorbol esters, suggesting a coupling between arginine uptake and NO synthesis through a PKC-dependent mechanism. However, arginine supplementation in the medium (10mM) failed to prevent the inhibitory action of Ang II on NO synthesis. These findings suggest that although Ang II inhibits concomitantly arginine transport and NO synthesis in SMCs, the reduction of NO synthesis is not associated with alterations in the cellular transport of arginine.

Readmission in unstable angina.

To determine the characteristics of patients re-admitted after unstable angina (UA) pectoris, 120 consecutive patients hospitalized due to primary UA pectoris were prospectively studied 22 +/- 3 months after discharge. The patients were grouped based on the readmission rate. Those in group A (50) had recurrent admissions (mean 2.6, range 2 to 5). Seventy patients (group B) did not have readmissions during the follow-up period. All patients underwent coronary angiogram and symptoms-limited exercise stress test before discharge. The univariate characteristics for readmission were: age over 70 years (p = 0.02), nondiagnostic exercise stress testing (p = 0.03), angiographically diffuse coronary artery disease (p = 0.004), and non-interventional management (P < 0.001). Patients readmitted had increased incidence of myocardial infarction (p = 0.004) but similar survival at 2 years. By regression analysis, important variables for readmission were non-interventional management (Chi-Square = 7.6, p = 0.01), non diagnostic treadmill test (Chi-Square = 6.9, p = 0.03) and diffuse coronary artery disease (Chi-Square = 6.2, p = 0.04). It is concluded that in the interventional era the most important factor for readmission after primary UA pectoris is non-interventional management. Coronary revascularization should not be denied solely on the basis of age.

[Enalapril reduces the degree of left ventricular remodeling after acute myocardial infarction and reduces the incidence of arrhythmia in ischemic disease]. / Enalapril reduce el grado de remodelamiento del ventrículo isquierdo después de un infarto agudo de miocardio y reduce la incidencia de arritmias en la enfermedad isquémica.

The present study shows that enalapril prevents the excessive remodeling of the left ventricle after acute myocardial infarction. This randomized and double blind clinical study analysed 50 patients with an inferior myocardial infarction. The effect of enalapril was evaluated through cardiac volumes, ejection fraction, neurohormonal levels and incidence of the left ventricle disfunction after acute myocardial infarction. The patients treated with enalapril showed a significant reduction on the values of nor-epinefrine, angiotensine II, natriuretic hormone and vasopressine, four weeks after initiation of treatment. The ejection fraction and the level of the wall movement was more favourable, four weeks after infarction, in the group treated with enalapril. The incidence of congestive heart failure and arrhythmias was lower in the group treated with enalapril. So, we conclude that enalapril is a drug that prevents the excessive remodelling of the left ventricle after an acute myocardial infarction.

Opportunistic invasion of the heart in Hispanic patients with acquired immunodeficiency syndrome.

One hundred consecutive patients who died of the acquired immunodeficiency syndrome (AIDS) were studied with an emphasis on the heart. Thirty-two patients showed pathologic changes. The pathologic findings included infection by Histoplasma capsulatum, Toxoplasma gondii, Mycobacterium tuberculosis, cytomegalovirus. Cryptococcus neoformans, and atypical mycobacteria. Noninfectious pathologic findings included nonspecific myocarditis, focal necrosis, focal fibrosis, and acute subendocardial infarction.

Transient elevation of pulmonary arterial pressure induced by sublingual angiotensin converting enzyme inhibitors.

Twelve patients with ischemic heart disease had complete left and right catheterization before and after sublingual captopril. Hemodynamic measurements were ten (10) minutes apart and were monitored for thirty (30) minutes. The heart rate increased from 70 +/- 13 to 76 +/- 11 beats/minute (P = .04). There was no change in the arterial blood pressure, although the systemic vascular resistance decreased from 1500 +/- 400 to 1026 +/- 480 dynes-sec-cm-5 (P < .0001). The pulmonary artery pressure was increased 15 +/- 6 to 25 +/- 5mmHg (P = .005) and the pulmonary vascular resistance increased from 288 + 160 to 376 + 160 dynes-sec-cm-5 (P < .0001). The wedge pressure increased from 7 +/- 2 to 14 +/- 3 mmHg (P = .05). The cardiac output (CO) increased from 5.06 +/- 1.06 to 578 +/- 1.58 Lt/min. (P.05 =. The left ventricular end diastolic volume (LVEDV) increased from 128 +/- 40 to 145 +/- 37cc)P = .002), without change in the end systolic volume (ESV). The ejection fraction (EF) increased from 56 +/- 3 to 61 +/- 4% (P = .02). These pressure changes appeared at two (2) minutes and disappeared after thirty (30) minutes. The study shows that, sublingual captopril produces a transient elevation of the pulmonary artery pressure and resistance.

Lack of interaction of angiotensin converting enzyme inhibitors with muscarinic and neuropeptide Y receptors.

In studies conducted in patients undergoing cardiac catheterizations, some hemodynamic changes were observed after the acute sublingual administration of the angiotensin converting enzyme inhibitors (ACEI) captopril, enalapril, and lisinopril. These changes consisted of an increase in pulmonary artery pressure, pulmonary vascular resistance (PVR) and induction of hypoxia. The pressure changes were transitory and disappeared after 25 min. The possible mechanisms involved in these changes may relate to interactions of the ACEI with peripheral receptor systems for hormones and neurotransmitters. We have thus undertaken the task of evaluating the potential effect of ACEI on biological receptor molecules. We have begun with studies on muscarinic receptors, and the recently characterized neuropeptide Y (NPY) receptors of endothelial cells. Equilibrium binding assays with 3H-QNB have been conducted for muscarinic receptors using rat brain synaptosomes, due to its expression of multiple muscarinic receptors subtypes. In addition 125BH-NPY binding assays were conducted on intact adrenal medullary endothelial cells. Enalapril and captopril, 10(-7) to 10(-3) M, were not able to produce significant inhibition of either muscarinic or NPY receptor probes. The paradoxical changes elicited by sublingual ACEI seems not to involve interaction with muscarinic or NPY receptors.

Effects of enalaprilat on hemodynamics and ventricular activation duration in hypertensive patients with left ventricular hypertrophy: clinical evidence of improved excitation-contraction coupling with angiotensin converting enzyme inhibition in human hypertension.

Hypertension is a major risk factor for the development of heart failure. Despite significant progress in our knowledge of the physiopathology of heart failure, the cause for decompensation in patients with left ventricular hypertrophy (LVH) is still obscure. The angiotensin converting enzyme inhibitor enalaprilat has been found to improve electromechanical coupling of heart cells in animal models. To assess the effects of enalaprilat on ventricular electromechanical coupling in humans, we studied the His bundle electrograms and hemodynamics in 22 hypertensive patients with LVH. Patients received either 2.5 mg enalaprilat or saline placebo intravenously in a double-blind protocol. There were no significant changes in heart rate, and atrioventricular and His-Purkinje conduction times. Ventricular activity duration was reduced from 110 +/- 11 msec to 88 +/- 13 msec after enalaprilat administration (P < .01). Enalaprilat decreased peak-systolic and end-diastolic left ventricular pressures, and arterial and pulmonary pressures, as well as pulmonary and systemic vascular resistances. End-systolic wall stress decreased 18% (P < .01), ejection fraction increased 11% (P < .01), and end-diastolic pressure-volume ratio decreased 50% (P < .001) after enalaprilat administration. There were no significant changes in these parameters after saline infusion. It is concluded that enalaprilat reduces ventricular activation duration and improves ventricular performance in hypertensive patients with LVH. Data suggest that enalaprilat significantly improves excitation-contraction coupling in these patients.

Cocaine induced myocardial ischemia.

We report a case of myocardial ischemia induced by cocaine. The ischemia probably induced by coronary artery spasm was reversed by nitroglycerin and calcium blocking agents.