Alcohol abuse can affect more than the heart and the liver. Many observers often do not appreciate the complex and differing aspects of alcohol’s effects in pathophysiologies that have been reported in multiple organs. Chronic alcohol abuse is known to be associated with pathophysiological changes that often result in life-threatening clinical outcomes, e.g., breast and colon cancer, pancreatic disease, cirrhosis of the liver, diabetes, osteoporosis, arthritis, kidney disease, immune system dysfunction, hypertension, coronary artery disease, cardiomyopathy, and can be as far-reaching as to cause central nervous system disorders. In this review article, we will discuss the various organs impacted by alcohol abuse. The lack of clear guidelines on the amount and frequency of alcohol intake, complicated by personal demographics, make extrapolations to real-life practices at best difficult for public health policy-makers.

Previous studies have demonstrated positive-inotropic effects of calcitonin gene-related peptide (CGRP), but the mechanisms remain unclear. Therefore, two experiments were performed to determine the physiological correlates of the positive-inotropic effects of CGRP. Treatments designed to antagonize the effects of physiologically active CGRP_1–37 included posttreatment with CGRP_8–37 and pretreatment with LY-294002 (LY, an inhibitor of phosphatidylinositol 3-kinase), 17β-estradiol (E), and progesterone (P) were also used to modulate the effects of CGRP_1–37. Experiment 1 was in vitro studies on sarcomeres and cells of isolated adult rat cardiac myocytes. CGRP_1–37, alone and in combination with E and P, decreased sarcomere shortening velocities and increased shortening percentages, effects that were antagonized by CGRP_8–37, but not by LY. CGRP_1–37 increased resting intracellular calcium ion concentrations and Ca²⁺ influxes, effects that were also antagonized by both CGRP_8–37 and LY. Experiment 2 was in vivo studies on left ventricular pressure-volume (PV) loops. CGRP_1–37 increased end-systolic pressure, ejection fraction, and velocities of contraction and relaxation while decreasing stroke volume, cardiac output, stroke work, PV area, and compliance. After partial occlusion of the vena cava, CGRP_1–37 increased the slope of the end-systolic PV relationship. CGRP_8–37 and LY attenuated most of the CGRP-induced changes. These findings suggest that CGRP-induced positive-inotropic effects may be increased by treatments with estradiol and progesterone and inhibited by LY. The physiological correlates of CGRP-induced positive inotropy observed in rat sarcomeres, cells, and intact hearts are likely to reveal novel mechanisms of heart failure in humans.

Alcohol abuse causes 79,000 deaths stemming from severe organ damage in the United States every year. Clinical manifestations of long-term alcohol abuse on the cardiac muscle include defective contractility with the development of dilated cardiomyopathy and low-output heart failure; which has poor prognosis with less than 25% survival for more than three years. In contrast, low alcohol consumption has been associated with reduced risk of cardiovascular disease, however the mechanism of this phenomenon remains elusive. The aim of this study was to determine the significance of apoptosis as a mediating factor in cardiac function following chronic high alcohol versus low alcohol exposure. Adult rats were provided 5 mM (low alcohol), 100 mM (high alcohol) or pair-fed non-alcohol controls for 4–5 months. The hearts were dissected, sectioned and stained with cresyl violet or immunohistochemically for caspase-3, a putative marker for apoptosis. Cardiomyocytes were isolated to determine the effects of alcohol exposure on cell contraction and relaxation. High alcohol animals displayed a marked thinning of the left ventricular wall combined with elevated caspase-3 activity and decreased contractility. In contrast, low alcohol was associated with increased contractility and decreased apoptosis suggesting an overall protective mechanism induced by low levels of alcohol exposure.

Heart failure can be caused by pro-hypertrophic humoral factors such as angiotensin II (Ang II), which regulates protein kinase activities. The intermingled responses of these kinases lead to the early compensated cardiac hypertrophy, but later to the uncompensated phase of heart failure. We have shown that although beneficial, cardiac hypertrophy is associated with modifications in ion channels that are mainly mediated through mitogen-activated protein (MAP) kinase and phosphatidylinositol 3-kinase (PI3K) activation. This study evaluates the control of L-type Ca²⁺current (I_Ca,L) by the Ang II/PI3K pathway in hypertrophied ventricular myocytes from volume-overload rats using the perforated patch-clamp technique. To assess activation of the I_Ca,Lin cardiomyocytes, voltages of 350 ms in 10 mV increments from a holding potential of –85 mV were applied to cardiocytes, with a pre-pulse to –45 mV for 300 ms. Volume overload-induced hypertrophy reduces I_Ca,L, whereas addition of Ang II alleviates the hypertrophic-induced decrease in a PI3K-dependent manner. Acute administration of Ang II (10⁻⁶ mol/L) to normal adult cardiomyocytes had no effect; however, captopril reduced their basal I_Ca,L. In parallel, captopril regressed the hypertrophy and inverted the Ang II effect on I_Ca,Lseemingly through a PI3K upstream effector. Thus, it seems that regression of cardiac hypertrophy by captopril improved I_Ca,Lpartly through PI3K.