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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Coronary artery occlusion results in the acute activation of the renin-angiotensin system and production of angiotensin II, a potent vasoconstrictor and positive inotropic agent. This has raised the possibility that angiotensin converting enzyme (ACE) inhibitors might be "cardioprotective" (that is, might attenuate myocardial injury, dysfunction and necrosis) in the setting of acute ischemia and infarction. Captopril, enalapril and ramipril have, in fact, been reported to acutely limit myocardial injury and necrosis in models of permanent coronary artery occlusion. The mechanisms responsible for this cardioprotection are complex, but include favorable alterations in myocardial oxygen supply/demand, and, in some instances, inhibition of bradykinin metabolism and/or increased prostaglandin synthesis. Other studies, however, have failed to document a reduction in infarct size with ACE inhibitor treatment. Results obtained in models of coronary occlusion/reperfusion have also been mixed. In models of brief transient ischemia not associated with necrosis, captopril and zofenopril have consistently been found to attenuate postischemic contractile dysfunction of the viable but "stunned" myocardium during the early hours following relief of ischemia. In contrast, there is no consensus on the effects of enalapril on the stunned myocardium: both positive and negative results have been obtained. Similar disparity has been reported in models of more prolonged ischemia/reperfusion resulting in subendocardial necrosis: some studies have reported myocardial salvage, while others have provided disturbing evidence of apparent exacerbation of myocardial necrosis with captopril and enalapril therapy. Thus, after a decade of investigative effort, the question of whether ACE inhibitors are "cardioprotective" in the setting of acute myocardial ischemia and infarction remains unresolved. Nonetheless, clinical protocols are in progress to assess the effects of early ACE inhibitor treatment in patients with acute myocardial infarction.
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PMID:"Cardioprotection" by ACE-inhibitors in acute myocardial ischemia and infarction? 835 29

A patient with acute esophageal variceal bleeding developed fatal rhabdomyolysis during treatment with a continuous intravenous infusion of vasopressin. Signs of ischemia, including mottling of skin and painful extremities, preceded the development of the characteristic electrolyte abnormalities and cardiac arrhythmias. No other recognized causes of rhabdomyolysis were identified on retrospective review of the hospital course. There are several factors which might promote a peripheral ischemic response to vasopressin in the bleeding cirrhotic patient, including altered resting hemodynamics, increased resting sympathetic tone, impaired vasodilation as a compensatory response to vasopressin, and reduced hepatic drug clearance. Idiosyncratic factors involving vasopressin receptor affinity and distribution, vasopressin-associated vasodilation in some vascular beds, and the effect of vasopressin on the renin-angiotensin system may further contribute to impaired tissue perfusion. These multiple overlapping factors probably lead to rhabdomyolysis in a minority of patients receiving vasopressin infusion.
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PMID:Rhabdomyolysis associated with the use of intravenous vasopressin. 843 51

This review summarizes in the first part the action of adenosine on the kidney. In the second part we discuss the pathophysiological consequences and the possibilities of a pharmacological intervention to improve impaired kidney function. Adenosine causes vasoconstriction in the kidney and reduces glomerular filtration rate (GFR). This action is enhanced in proportion to elevated plasma renin activity. Chronic elevation of ureteral pressure enhances and reduction of renal perfusion pressure attenuates adenosine-induced vasoconstriction. From the kidney-specific relationship between renal blood flow and tubular electrolyte transport the concept is developed which ascribes adenosine a role of a mediator that is essentially contributing to the homeostatic regulation of kidney function. The accumulation of adenosine in the kidney tissue after ischemia or after administration of nephrotoxic substances led to the hypothesis that adenosine is an important intrarenal factor in the pathogenesis of acute renal failure. The possibility to antagonize adenosine actions in the kidney with theophylline was used successfully in a number of experimental studies in acute renal failure and most recently in a study in humans after contrast media administration. Adenosine actions mediated via membrane receptors must be separated from adenosine actions in the cell to increase ATP tissue content. The concept of the "University of Wisconsin" (UW) solution to improve the energy state of the tubular cells appears to be successful, however, we propose that the potential dangerous adenosine actions in the kidney, especially during the reperfusion phase may be antagonized by the administration of theophylline.
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PMID:[Renal effects of adenosine: possible consequences for kidney transplantation]. 846 19

Dynamic exercise causes an increase in circulating blood levels of renin and vasopressin (AVP), yet the afferent mechanisms responsible for release of renin and AVP during exercise are poorly understood. Partial ischemia of active skeletal muscle induces a reflex pressor response, termed the muscle metaboreflex. Does muscle metaboreflex activation induce release of renin and AVP? The muscle metaboreflex was activated in conscious, chronically instrumented dogs during mild treadmill exercise (3.2 km/h, 0% grade) via graded partial occlusion of terminal aortic blood flow. Decreasing hindlimb perfusion to 40% of the control level during exercise significantly increased systemic arterial pressure (SAP) and heart rate (HR) from 103.4 +/- 2.4 to 166.7 +/- 4.2 mmHg and from 111.6 +/- 9.9 to 141.9 +/- 3.9 beats/min, respectively. However, only small nonsignificant changes in arterial plasma renin activity and AVP concentration occurred [control: renin = 0.46 +/- 0.8 ng angiotensin I (ANG I).ml-1.h-1, AVP = 0.53 +/- 0.17 pg/ml; metaboreflex activation: renin = 0.77 +/- 0.33 ng ANG I.ml-1.h-1, AVP = 1.09 +/- 0.34 pg/ml]. The experiments were repeated after ganglionic blockade (hexamethonium 10 mg/ml and atropine 0.2 mg/ml iv) to attenuate the reflex increase in SAP. In this setting, metaboreflex activation caused SAP to increase from 91.6 +/- 4.3 to only 114.7 +/- 6.8 mmHg and the reflex tachycardia was abolished (153.7 +/- 5.8 to 159.3 +/- 6.1 beats/min, P > 0.05). With the reflex pressor response markedly attenuated, AVP increased from 2.53 +/- 0.81 to 34.38 +/- 6.59 pg/ml with muscle metaboreflex activation, whereas no significant changes in renin activity occurred.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Muscle metaboreflex control of vasopressin and renin release. 849 56

Left ventricular hypertrophy is considered to be an independent risk factor giving rise to ischemia, arrhythmias, and left ventricular dysfunction. Slow movement of intracellular calcium contributes to the impaired contraction and relaxation function of hypertrophied myocardium. Myofibril content may also be shifted to fetal-type isoforms with decreased contraction and relaxation properties in left ventricular hypertrophy. Myocyte hypertrophy and interstitial fibrosis are regulated independently by mechanical and neurohumoral mechanisms. In severely hypertrophied myocardium, capillary density is reduced, the diffusion distance for oxygen, nutrients, and metabolites is increased, and the ratio of energy-production sites to energy-consumption sites is decreased. The metabolic state of severely hypertrophied myocardium is anaerobic, as indicated by the shift of lactate dehydrogenase marker enzymes. Therefore, the hypertrophied myocardium is more vulnerable to ischemic events. As a compensatory response to severe cardiac hypertrophy and congestive heart failure, the ADP/ATP carrier is activated and atrial natriuretic peptide is released to increase high-energy phosphate production and reduce cardiac energy consumption by vasodilation and sodium and fluid elimination. However, in severely hypertrophied and failing myocardium, vasoconstrictor and sodium- and fluid-retaining factors, such as the renin-angiotensin system, aldosterone, and sympathetic nerve activity, play an overwhelming role. Angiotensin-converting enzyme inhibitors (ACEIs) are able to prevent cardiac hypertrophy and improve cardiac function and metabolism. Under experimental conditions, these beneficial effects can be ascribed mainly to bradykinin potentiation, although a contribution of the ACEI-induced angiotensin II reduction cannot be excluded.
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PMID:Substrate metabolism, hormone interaction, and angiotensin-converting enzyme inhibitors in left ventricular hypertrophy. 852 2

Black kidney transplant recipients have worse graft survival than white recipients. Speculation regarding etiology has focused on differences in human lymphocyte antigens (HLA). Some suggest that improvements in graft survival would be obtained if donor and recipient race were matched. We reviewed 236 cadaver transplants performed over 9 years at a single center using an HLA-match-driven allocation system and a uniform immunosuppressive protocol to determine the impact of donor race on graft survival. A multivariate analysis of graft survival using patient race, sex, age, transplant number, current and maximum plasma renin activity, donor race, cold ischemia time and HLA mismatch, the need for dialysis, and the presence of rejection as independent variables. Sixty percent of recipients were black, and 82% were primary transplants; 28 kidneys (12%) were from black donors. The 112 patients with the same race donor had identical 5-year graft survival as the 124 who had a different race donor (40%; P = 0.1726). The 5-year survival of the 88 white recipients of white donor organs was better than that of the 120 black recipients of white donor organs (54% vs. 42%, respectively; P = 0.0398). Black recipients (t1/2 = 37 months) did worse than white recipients (t1/2 = 60 months) regardless of organ source (P = 0.023). In the multivariate analysis, neither donor nor recipient race were an independent variable in predicting graft survival. Rejection (RR = 2.9) and the need for dialysis on the transplant admission (RR = 4.1) were the only factors that predicted poor survival. Black recipients had more rejection (P = 0.04) but not more need for dialysis posttransplant regardless of donor race. Donor race did not affect graft survival in this series. The effect of recipient race on graft survival was due to an increased incidence of rejection episodes in black recipients, which was independent of HLA mismatch. These data suggest that improvements in immunosuppression, not changes in allocation, are needed to improve graft survival.
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PMID:Donor race does not affect cadaver kidney transplant survival--a single center experience. 854 64

Hypertension can be a cause as well as a consequence of renal disease. Fluid overload or activation of the renin angiotensin system by glomerular ischemia leads to an elevation of systemic blood pressure in acute as well as chronic renal disease. Furthermore in the latter disorder an increased activity of the sympathetic nervous system as well as metabolic disorders contribute to hypertension. Accordingly antihypertensive therapy in patients with renal insufficiency is diverse. Additionally in chronic kidney disease one has to consider the variable effects of different antihypertensive drugs on intrarenal hemodynamics.
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PMID:[Antihypertensive therapy in renal failure]. 857 52

Coronary reserve plays an important role in myocardial oxygen supply. During rest, oxygen consumption is near to maximal. An increase in myocardial oxygen demand can only be covered by an increase in coronary flow by dilation of coronary vessels. The maximal achievable rise in coronary blood flow is called coronary reserve. Coronary reserve is not only enhanced in patients with coronary artery disease but also in patients with disorders of coronary microcirculation for example in arterial hypertension. The following review will deal especially with disorders of the microcirculation in arterial hypertension. The impairment of coronary reserve is a result of structural and functional alterations. Structural alterations include an increase in media wall thickness of the small coronary arteries and a reduction of coronary capillaries. Extravascular myocardial forces which determine coronary resistance include myocardial hypertrophy and qualitative changes of myocardium like interstitial and perivascular fibrosis. The role of functional alterations like endothelial related vasomotion is discussed. The renin-angiotensin system modulates the growth of the small muscle cells of the vessels and induces protooncogenes and other growth factors. Therefore the renin-angiotensin system may also play an important role in hypertensive remodeling. Hypertensive coronary microangiopathy is diagnosed by exercise stress test and ST-segment-monitoring over 24 hours to show myocardial ischemia. Also nuclear medicine technics can be used if conventional methods of showing ischemia don't work. The diagnosis is definite if the determination of coronary reserve shows that the maximal coronary blood flow is not achieved. Coronary flow can be measured by the argon-gas-method, the thermodulation-technic or by the doppler-method. Also by nuclear medicine technics (PET) the coronary flow reserve can be determined. The advantages of these methods are discussed. In experimental studies calcium-channel-blockers, ACE-inhibitors and moxonidine showed an increase in density of capillaries and also a reduction of myocardial hypertrophy, which both result in an improvement of coronary reserve. Clinical studies of our group demonstrate that coronary microangiopathy in hypertensives can be improved by calcium-channel-blockers and ACE-inhibitors after one year treatment. Beta-receptor-blockers show no clear improvement of coronary reserve. It has to be shown by further studies whether the improvement of coronary reserve is more important for prognosis than the regression of myocardial hypertrophy.
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PMID:[Coronary microangiopathy in hypertensive heart disease: pathogenesis, diagnosis and therapy]. 858 95

Renovascular disease is the leading cause of surgically-curable arterial hypertension and one of the few cause of reversible chronic renal failure, but its exact prevalence remains unknown. Progression of atheromatous disease occurs in 50% of cases and it may result in bilateral stenosis (25%) or total occlusion (15%). By now, the main aim of renal revascularization is retrieval of impaired function or prevention of renal failure rather than control of hypertension. However, renal functional deterioration may result from cholesterol embolism or glomerulosclerosis in addition to ischemia. Correction of post-proximal stenosis is obtained by both surgery and percutaneous angioplasty. In favor of angioplasty are a higher acceptability and a modestly better cost-benefit ratio. Surgery may be preferred when the stenosis is proximal, complex or associated with aortic disease; in addition, analysis of published (mostly uncontrolled) series suggest that beneficial renal functional outcome is slightly better following surgery. Importantly, both diagnosis and prognosis of ischemic nephropathy are difficult to establish. Various predictors of recovery (renal size, renal vein renin ratio, alteration in scintigrams, angiography or biopsy) were shown to fail on an individual basis. Further controlled studies based on reliable methods of measuring renal function are warranted.
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PMID:[Preservation of renal function by revascularization in renovascular disease]. 858 40

Hypertension after renal transplantation continues to affect 50% or more of patients, despite use of modern immunosuppressive regimens. Relationships between poor control of blood pressure and reduced chronic allograft survival have been clearly demonstrated, and are analogous to the well-known acceleration of progressive renal disease by coexisting hypertension. It is likely, although to date it has not been formally proven by prospective study, that effective blood pressure control has a beneficial effect on chronic allograft outcome, as in progressive dysfunction of native kidneys. A further key question is whether differing classes of antihypertensive therapy may have differing effects on long-term graft outcome. It has been proposed that glomerular hypertension, hyperfiltration and hypertrophy, secondary both to inadequate nephron mass and to loss of functioning nephrons, may contribute to chronic allograft failure. If this is true, then use of converting enzyme inhibitors may particularly benefit long-term graft outcome. However, post-transplant hypertension in cyclosporine-treated patients is associated with sodium retention and renin system suppression, and a relative lack of renoprotective action of ACE inhibitors might be predicted in this context. An alternative hemodynamic factor underlying chronic allograft failure is glomerular ischemia, secondary to the vascular changes associated with chronic rejection and to cyclosporine-related afferent arteriolar vasoconstriction. In this setting, calcium channel blockers which lower systemic blood pressure in combination with afferent arteriolar vasodilatation may improve long-term allograft outcome. New strategies with a similar rationale include endothelin receptor antagonists and neutral endopeptidase inhibitors such as candoxatril, which in acute experimental and clinical studies reverse cyclosporine-induced reductions in renal blood flow and glomerular filtration rate. Long-term prospective controlled comparative studies are needed to assess the effect of all these differing therapeutic approaches on chronic allograft outcome.
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PMID:Does antihypertensive therapy modify chronic allograft failure? 858 70


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