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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although hypertension is associated with increased risk of sudden cardiac death, the mechanisms involved remain enigmatic. Little is known about hemodynamic and plasma catecholamine concentration changes during coronary artery occlusion in hypertensive subjects. To study this, 30 pigs were implanted with catheters in the aorta and a silk snare around the left anterior descending coronary artery that could later be pulled to permanently occlude the artery. Perinephritic hypertension was induced in 14 of the animals over 3 weeks by wrapping one kidney in silk followed by contralateral nephrectomy. Coronary artery occlusion (CAO) was carried out in all pigs in the conscious resting state. Ventricular fibrillation (VF) developed in 50% of each group within 15 min after coronary artery occlusion. The hypertensive VF group showed an increase in norepinephrine concentration of 112 +/- 46%; a significantly greater increase than the intact VF group, which showed a 29 +/- 7% increase in norepinephrine concentration 5 min after coronary artery occlusion (p < 0.05).
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PMID:Plasma norepinephrine increased during coronary occlusion in hypertensive pigs that developed ventricular fibrillation. 897 45

The objective of the study was to determine if male subjects with coronary atherosclerotic heart disease (CHD) without major CHD risk factors have hyperinsulinemia and related metabolic changes. Previous studies suggested that hyperinsulinemia is a CHD risk factor, but they did not entirely exclude concurrent metabolic abnormalities. A prospective, comparative, cross-sectional study in a tertiary care teaching hospital in Mexico City was conducted in 15 men who had suffered myocardial infarction 6 to 24 months before and had significant coronary occlusion on angiography. Control group was formed by 15 age-matched healthy men. None had hypertension, obesity, diabetes, gout, glucose intolerance or hyperlipidemia. Body mass index (BMI), waist/hip ratio (WHR), blood pressure (BP); oral glucose tolerance test (OGTT) with measurement of serum glucose, insulin and C-peptide every 30 min for 2 h, fasting serum cholesterol, triglycerides and uric acid, areas under curve (AUC) of glucose and insulin, insulin/glucose ratio and insulin sensitivity index were calculated. BMI, WHR and BP were similar in both groups. Fasting and post-load serum glucose and insulin concentrations were significantly higher in CHD than in control group (p < 0.01); fasting glucose 5.9 +/- 0.6 vs. 4.8 +/- 0.7 nmol/1, 2-h glucose 8.3 +/- 0.6 vs. 7.3 +/- 0.9 mmol/l, fasting insulin 17.5 +/- 1.2 vs. 15.3 +/- 1.7 pmol/l, 2 h insulin 448 +/- 108 vs. 282 +/- 87 pmol/l in CHD and control group, respectively. AUC of glucose, AUC of insulin, insulin/glucose ratio, post load C-peptide, serum cholesterol, triglycerides and uric acid levels were also significantly higher in CHD than in healthy controls. Insulin sensitivity index was significantly lower in patients with CHD (27.7 +/- 8.3) than in healthy control subjects (73.9 +/- 18) (p < 0.001). Patients with CHD have hyperinsulinemia and subtle metabolic abnormalities related with insulin resistance even in absence of overt risk factors.
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PMID:Hyperinsulinemia in patients with coronary heart disease in absence of overt risk factors. 907 98

It is too often deduced that myocardial infarction is due to coronary occlusion and that subsequent death needs no other explanation. But the great majority of myocardial infarctions are not fatal, whether treated or untreated. There is, of course, some relation to the size of the infarct and the presence or absence of complicating conditions such as diabetes mellitus or hypertension, but little attention has been directed at the myriad of other events and processes influencing the clinical course. Examples include the exact anatomic territory infarcted and whether it includes the sinus node or AV node or important neuroreceptors; whether many small arteries are occluded (especially downstream of narrowed main coronary branches); whether the heart is hypertrophied, dilated, infected, or infiltrated; and whether there may be intracardiac, extracardiac, or intracranial neuropathological conditions that could destabilize cardiac electrical activity. It is now known that apoptosis plays a major role in myocardial infarction or ischemia, but it also occurs within the heart completely independently of infarction. There is also the vexing dilemma that an effective coronary collateral circulation, which is determined primarily by transanastomotic pressure gradient, is made less effective by exactly those treatments that reestablish flow in an occluded coronary artery. Since thrombolysis and angioplasty are automatically considered urgent treatment for an occluded coronary artery, it is prudent to remember the complex causes that determine whether the patient lives or dies.
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PMID:Complex causes of fatal myocardial infarction. 931 66

Sudden cardiac death is the leading cause of death in industrialized countries. It is most frequently due to ventricular tachyarrhythmias occurring in the presence of coronary heart disease, but mechanisms linking sudden death to coronary atherosclerosis are still unclear. In autopsy studies of sudden death patients, the incidence of acute thrombotic coronary occlusions has varied between 4 and 74%. In over 600 consecutive patients with implantable cardioverter-defibrillators, we observed that appropriate shocks for electrogram-verified ventricular tachyarrhythmias was only very rarely followed by signs of acute myocardial infarction (< 3% of cases), not supporting the coronary occlusion theory of fatal arrhythmias. Cellular hypertrophy compensating for cell loss due to ischemia, intraventricular hypertension, cardiomyopathy, and myocarditis might play a role in arrhythmogenesis as evidenced by the fact that experimental induction and regression of hypertrophy are paralleled by changes in the inducibility of ventricular tachyarrhythmias. Atherogenic hyperlipidemias are associated with a systemic inflammatory response manifested by leukocytosis (lymphocytosis) and complex upregulations of proinflammatory-prothrombotic mediators, such as platelet-activating factor, cytokines, and hemostasis factors. The diurnal regulation of these mediators parallels circadian rhythms of coronary morbidity and mortality. Some upregulated mediators have been shown to exert direct arrhythmogenic effects. The potential contribution of hyperlipidemia-associated inflammatory factors to arrhythmogenesis is important, because it opens new molecular targets for antiarrhythmic drug design.
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PMID:Sudden cardiac death: still more questions than answers. 947 68

Angiotensin-converting enzyme (ACE) inhibitors increase the production of nitric oxide (NO) and prostacyclin and open Ca2+-activated K+ channels. The effects of these actions of ACE inhibitors on infarct size were investigated in open-chest dogs subjected to myocardial ischemia and reperfusion. Infarct size was assessed 6 hours after the onset of reperfusion, subsequent to 90 minutes of occlusion of the left anterior descending coronary artery. The ACE inhibitor cilazaprilat was administered into the coronary artery 10 minutes before coronary occlusion, and infusion was continued until 1 hour after reperfusion. The bradykinin and NO concentrations in coronary venous blood 10 minutes after the onset of reperfusion were significantly higher in dogs treated with cilazaprilat (3 microg x kg(-1) x min(-1)) than in control animals. Although there were no significant differences in collateral flow during ischemia, infarct size in the cilazaprilat group was smaller than that in the control group (15.1+/-3.0% versus 46.7+/-4.2% of the area at risk, P<0.0001). The infarct size-limiting effect of cilazaprilat was partially reduced by either N(G)-nitro-L-arginine methyl ester (an inhibitor of NO synthase) or iberiotoxin (a blocker of Ca2+-activated K+ channels) and was abolished by N(G)-nitro-L-arginine methyl ester plus iberiotoxin. Indomethacin (an inhibitor of cyclooxygenase) had no effect on the beneficial action of cilazaprilat. Inhibition of ACE thus reduced myocardial infarct size, an effect that was mediated by NO and the opening of Ca2+-activated K+ channels in canine hearts.
Hypertension 1998 Jun
PMID:Role of Ca2+-activated K+ channels in the protective effect of ACE inhibition against ischemic myocardial injury. 962 44

Capillaries are nonuniform thin tubes: The arteriolar and venular capillary portions express alkaline phosphatase (AP) and dipeptidyl peptidase IV (DPPIV), respectively. Differences in enzyme activities between arteriolar and venular capillary portions could be shown by staining sections of cardiac tissues for AP and DPPIV after coronary infusion of microspheres and by staining cultured endothelial cells that had been collected from coronary microvessels. Through use of a double staining method for AP and DPPIV, adaptive changes in the capillary network were studied in rat hearts exposed to cold, exercise, hypertension, chronic coronary occlusion, and transient coronary occlusion followed by reperfusion. Two patterns could be seen in the adaptations of the ventricular capillary network. The increase in the venular capillary portions is accompanied by remarkable increases in capillary density and capillary-to-myocyte ratio. The increase in the arteriolar capillary portion seemed to be accompanied by a decrease or only a limited increase in capillary density in stressed hearts. The increase in the total capillary density improves the capacity for oxygen transport to tissues with a high tissue perfusion and a short diffusion distance for oxygen. The increase in the arteriolar capillaries may also improve oxygen transport by increasing the arterial blood perfusing the tissue. This seems, however, a compensation for the limited angiogenesis: The alleviation of stresses, such as pharmacological treatment of the hypertrophied heart and reperfusion after transient ischemia, increases venular capillary portions and capillary density. These changes are discussed with immunohistochemical observations of rapid and prolonged expressions of angiogenic growth factors.
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PMID:Adaptive changes in the capillary network in the left ventricle of rat heart. 975 39

Moderate use of alcohol has shown protective effects in coronary artery disease, while excessive use has been associated with cardiomyopathy and hypertension. Since alcohol is a vasodilator, we postulated that it might have protective effects when administered acutely in the setting of ischemia/reperfusion. Therefore, we studied the acute effects of alcohol on myocardial infarction in a rabbit model. Anesthetized, open chest rabbits were subjected to a 30 minute coronary artery occlusion followed by 4 hours of reperfusion. Rabbits were randomized to a control group (n = 20), receiving an infusion of 10 ml normal saline, intravenously, over 10 minutes via a Harvard pump, or an alcohol group (n = 20), receiving a diluted solution of 100% ethanol (1 ml/kg diluted in normal saline to 10 ml total solution) infused in a similar fashion. This infusion regimen resulted in an average blood alcohol level of 110 mg/dl (range 77-129) tested in five rabbits within the study. Ten minutes after in fusion, a marginal branch of the circumflex artery was occluded. Regional myocardial blood flow during coronary occlusion and reperfusion was measured using radioactive microspheres. Myocardial ischemic area at risk (AR) was assessed by blue dye injection and myocardial necrosis (AN) by triphenyltetrazolium chloride (TTC) staining. The mean regional coronary blood flow in ischemic tissue was 0.04 +/- 0.01 ml/min/g in the control group versus 0.03 +/- 0.01 ml/min/g in the experimental group (p = NS) and averaged 1.74 ml/min/g (control) to 1.98 ml/min/g (alcohol) in the nonischemic tissue. All rabbits received comparable ischemic insult: Collateral blood flow and AR were similar in both groups. An overall analysis showed no significant reduction in infarct size (expressed as the percent of necrotic tissue within the area at risk) in the alcohol group (23 +/- 3%) compared with the control group (27 +/- 4%). In conclusion, alcohol did not reduce infarct size in the rabb it model.
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PMID:Acute Ethanol Does Not Protect Against Ischemic/Reperfusion Injury in Rabbit Myocardium. 1061 80

The tissue kallikrein-kinin system is present in the heart, and kinin has been shown to have cardioprotective effects. In this study, we investigated the potential role of tissue kallikrein in myocardial ischemia/reperfusion injury through adenovirus-mediated human kallikrein gene delivery. One week after gene delivery, the rats were subjected to a 30-minute coronary occlusion followed by a 2-hour reperfusion. Kallikrein gene delivery caused significant decreases in the ratio of infarct size to ischemic area at risk (from 69.6% to 44.5%, n=10 and 8, P<0.01) and in the incidence of ventricular fibrillation (from 64.3% to 16.7%, n=14 and 24, P<0.01) compared with the group injected with control adenovirus. Kallikrein gene delivery also attenuated programmed cell death in the ischemic area compared with the control area as assessed with the terminal deoxynucleotidyl transferase-mediated nick end labeling assay (n=6, P<0.01). Icatibant, a specific bradykinin B(2) receptor antagonist, abolished these kallikrein-mediated beneficial effects. The expression of human tissue kallikrein mRNA was identified in rat heart, kidney, lung, liver, and adrenal gland. After kallikrein gene delivery, cardiac kinin and cGMP levels were significantly elevated compared with the control (29.6+/-12.7 versus 6.1+/-2.1 pg/mg protein, n=7, P<0.01; 1.30+/-0.06 versus 0.86+/-0.09 pmol/mg protein, n=5, P<0.05). These results indicate that kallikrein gene delivery protects against myocardial infarction, ventricular arrhythmias, and apoptosis in ischemia/reperfusion injury via kinin-cGMP signal pathway. The successful application of this technology may have potential therapeutic value in the treatment of coronary artery diseases.
Hypertension 2000 Jan
PMID:Kallikrein gene delivery attenuates myocardial infarction and apoptosis after myocardial ischemia and reperfusion. 1064 70

Atherosclerosis is manifested as coronary artery disease (CAD), ischemic stroke and peripheral vascular disease. Moderate alcohol consumption has been associated with reduction of CAD complications. Apparently, red wine offers more benefits than any other kind of drinks, probably due to flavonoids. Alcohol alters lipoproteins and the coagulation system. The flavonoids induce vascular relaxation by mechanisms that are both dependent and independent of nitric oxide, inhibits many of the cellular reactions associated with atherosclerosis and inflammation, such as endothelial expression of vascular adhesion molecules and release of cytokines from polymorphonuclear leukocytes. Hypertension is also influenced by the alcohol intake. Thus, heavy alcohol intake is almost always associated with systemic hypertension, and hence shall be avoided. In individuals that ingest excess alcohol, there is higher risk of coronary occlusion, arrhythmias, hepatic cirrhosis, upper gastrointestinal cancers, fetal alcohol syndrome, murders, sex crimes, traffic and industrial accidents, robberies, and psychosis. Alcohol is no treatment for atherosclerosis; but it doesn't need to be prohibited for everyone. Thus moderate amounts of alcohol (1-2 drinks/day), especially red wine, may be allowed for those at risk for atherosclerosis complications.
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PMID:Alcohol and atherosclerosis. 1124 69

The classic dogma, still prevalent in cardiology, that the adult myocardium is a terminally differentiated tissue unable to produce new cardiomyocytes needs to be revised in light of recent results. In human and experimental animals there is now incontrovertible evidence that new myocytes are continuously generated throughout life in response to physiological and pathological stimuli. Moreover, the elucidation of mechanisms responsible for the hypertrophic response indicate similarity and overlap with the mechanisms involved in cell death by apoptosis as well as cell growth. During cardiac development, from birth to adulthood, there is a balance between the stimuli induce cell growth -by hypertrophy and hyperplasia- on one hand and those that induce programmed cell death on the other. In human and experimental animals it has been well documented that pathological conditions, such as diabetes and hypertension, can increase dramatically the rate of cell death. Moreover, high rates of cell death have been measured in normal adult human hearts and those of mice and rats. No surprisingly, these values increase significantly with age and high in senescence. By themselves, these high rates of normal cell death provide a very compelling argument in favor of cardiomyocyte regeneration. Without cell renewal, these rates of cell death would be incompatible with survival because the heart would disappear before early adulthood. As expected, direct measurement of rates of new cell formation in adult hearts demonstrate high rates of cell renewal that compensate for cell death. Thus, the heart is in continuous cellular turnover with new myocardial cells replacing the older ones. Experiments with fetal mouse cardiocytes shows that the retinoblastoma protein is responsible for the cardiocyte withdrawal from the cell cycle during development. The identification in the adult heart of a subpopulation of quiescent cells that have many of the characteristics of stem cells able to rapidly enter the cell cycle and generate new cardiocytes is yet another evidence that the heart continuously produces new cardiocytes to replace those that disappear either by apoptosis or necrosis.Surprisingly, stem cells other that those from the heart are able to produce new cardiocytes and repopulate the myocardium. We have used bone marrow stem cells injected into the border zone of post-coronary occlusion necrosis. Remarkably, these cells have proven to be very effective in generating new myocardium in the necrotic zone that is integrated to the rest of the muscle and irrigated by new vessels. These results demonstrate that stem cells provide a new avenue for the generation of new contractile tissue. This approach could prove useful in the treatment of chronic cardiac failure and post-ischemic necrosis.
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PMID:[Generation of new cardiomyocytes in the adult heart: Prospects of myocardial regeneration as an alternative to cardiac transplantation]. 1141 43


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