Reperfusing the myocardium - a damocles Sword.

Return of blood flow after periodic ischemia is often accompanied by myocardial injury, commonly known as lethal reperfusion injury (RI). Experimental studies have shown that 50% of muscle die of ischemia and another 50% die because of reperfusion. It is characterized by myocardial, vascular, or electrophysiological dysfunction that is induced by the restoration of blood flow to previously ischemic tissue. This phenomenon reduces the efficiency of the present modalities used to combat the ischemic myocardium. Moreover, despite an improved understanding of the pathophysiology of this process and encouraging preclinical trials of multiple agents, most of the clinical trials to prevent RI have been disappointing and leaves us at ground zero to explore newer approaches.

Stem Cell Therapy in Acute Myocardial Infarction: A Pot of Gold or Pandora's Box.

Stem cell therapy for conditions characterized by myocyte loss in myocardial infarction and heart failure is intuitively appealing. Stem cells from various sources, including heart itself in preclinical and animal studies, have shown the potential to improve the function of ventricular muscle after ischaemic injury. The clinical experience from worldwide studies have indicated the safety profile but with modest benefits. The predominant mechanisms of transplanted cells for improving cardiac function have pointed towards paracrine effects rather than transdifferentiation into cardiomyocytes. Thus, further investigations should be encouraged towards bench side and bedside to resolve various issues for ensuring the correct type and dosing of cells, time, and method of delivery and identify correct mechanism of functional improvement. An interdisciplinary effort at the scientific, clinical, and the government front will bring successful realization of this therapy for healing the heart and may convert what seems now a Pandora's Box into a Pot of Gold.

Coronary heart disease, hypertension, and angiotensinogen gene variants in Indian population.

Gene encoding components of the renin angiotensin system (RAS) have been implicated with the increased risk of cardiovascular disease (CVD). Two variants of the angiotensinogen (AGT) gene, M235T and T174M, have been shown to be associated with increased risk of hypertension. In the present study, we examined the association of these two polymorphisms and their synergistic interaction with the angiotensin I-converting enzyme (ACE) deletion homozygote genotype (D/D) on subjects with coronary heart disease (CHD) and hypertension. We studied 131 healthy individuals, 141 angiographically verified CHD patients, and 159 hypertensive subjects. The identification of the ACE and AGT gene polymorphisms was carried out using a PCR-based restriction endonuclease digestion method. There was no significant difference in the distribution of the M235T and T174M variants between the two test groups and the control group. Association was also not seen when analysis was carried out in patients when subgrouped according to the extent of the severity of the disease. In addition, the risk was not restricted to subjects carrying the D allele of the ACE gene and T235T of AGT. M235T and T174M variants do not contribute to the increased risk of CHD or hypertension in the Indian population.

Comparative analysis of RBC membrane lipids in thalassemia, and iron deficiency anemia in relation to hypochromia and oxidant injury.

The effect of an intrinsic defect in the red cell and pronounced hypochromia on oxidative damage to RBC membrane lipids was compared in beta-thalassemia and iron deficiency anemia (IDA), which have a varied etiology but equivalent low hemogiobin content. The study was planned to correlate the etiology of the disorders to the severity of lipid imbalance and RBC hemolysis in membranes of both the conditions. Results indicated a fall of lysophosphatidylcholine(LPC), phosphatidylethanolamine(PE) and the unsaturated to saturated fatty acid ratio in both conditions, while phosphatidylcholine(PC) increased only in thalassemia. However, irrespective of the disease, sphingomyelin(SM), total cholesterol and phospholipid levels elevated and the hydrogen peroxide stress test indicated increased susceptibility of both pathologic RBCs to peroxidation. Present findings indicate that IDA and thalassemla, allow for considerable amounts of oxidative damage to membrane lipids, irrespective of their etiologles, and thus point hypochromia as an important contributor for inducing lipid imbalance and RBC hemolysis.

ACE and AT1R gene polymorphisms and hypertension in Indian population.

The renin angiotensin system (RAS) controls intrarenal blood pressure and sodium balance, and is an important target for antihypertensive therapy. Several polymorphisms have been identified within genes encoding RAS that may contribute to the development of elevated blood pressure. The relevance of these polymorphisms in hypertension remains controversial. In this study we have examined 105 hypertensive subjects and 192 controls from the Indian population for I/D polymorphism of angiotensin I converting enzyme (ACE) and A(1166)C polymorphism of angiotensin II type I receptor (AT1R) genes by polymerase chain reaction (PCR) and PCR-based restriction enzyme analysis method, respectively. There was no significant difference in the distribution of ACE (I/I, I/D, and D/D) and AT1R (A/A and A/C) genotypes between controls and hypertensive subjects. D allele was significantly associated with an early onset of hypertension and although nonsignificant, the frequency was high in subjects with family history of cardiovascular disorders. C(1166) allele of AT1R did not correlate with the age of onset of hypertension and the frequency was low in subjects with family history. Thus no association was found between ACE and AT1R genotypes and hypertension. However the D allele can be used as a predictor of risk of hypertension in the Indian population.

Genes of renin angiotensin system and coronary heart disease.

Coronary constriction, proliferation of smooth muscle cells and arrhythmia are involved in the pathophysiology of coronary heart disease and its complications such as myocardial infarction and sudden death. All these effects are favoured by high angiotensin II levels. Angiotensin II is the main effector molecule of the renin angiotensin system and it acts through angiotensin II type receptors. Genetically determined differences in the expression of the components of this system could adversely affect angiotensin II concentration and subsequently heart. Consequently each component of this system represents a potential candidate in the etiology of cardiovascular disease. In this article we review the variation of the angiotensin I converting enzyme, angiotensin II type I receptor and angiotensinogen genes and their association with cardiovascular disease.

Effect of tense ascites on esophageal body motility and lower esophageal sphincter pressure.

BACKGROUND: Esophageal motility and lower esophageal sphincter (LES) pressure change with rapid changes in intraabdominal pressure (IAP); the response of these to slow change in IAP is not known. AIMS: To study esophageal body motility and LES pressures in patients with cirrhosis with tense ascites in the basal state and after paracentesis. METHODS: Twenty four patients with cirrhosis of liver and tense ascites and 13 with cirrhosis without ascites (controls) were studied. Basal intragastric (IGP) and LES pressures, and esophageal body response to water swallows, were recorded using a water perfusion system; IAP was measured in patients with ascites. In patients with ascites, the study was repeated twice: after paracentesis of two liters of fluid and after adequate control of ascites. RESULTS: Basal IGP (p = 0.002) and duration of esophageal contraction (p = 0.01) were lower in controls, but basal LES pressures were similar in the two groups. After control of ascites, IAP (p = 0.02) and IGP (p = 0.005) decreased; amplitude and duration of distal esophageal contraction decreased (p < 0.05). The frequency of high-amplitude waves also decreased (p = 0.04). LES pressure remained unaltered. CONCLUSIONS: Esophageal contraction duration is increased in the presence of ascites, and decreases after control of ascites; LES pressure is not affected by ascites.