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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The present studies describe the blood pressure lowering, and some other haemodynamic effects, of the potassium channel activator, BRL 38227 ((-) enantiomer of cromakalim, CAS 94470-67-4) in various animal models. BRL 38227 was a potent antihypertensive agent following oral administration to conscious spontaneously hypertensive rats, SHR, (0.038, 0.075 and 0.15 mg/kg), renal hypertensive cats (0.035 and 0.05 mg/kg) and renal hypertensive dogs (0.05 and 0.1 mg/kg). The (+) enantiomer of cromakalim (BRL 38226) was without effect on blood pressure in the conscious rat and cat confirming the stereospecific mode of action of this potassium channel activator. Tachycardia accompanied the antihypertensive effect of BRL 38227 in these models and in the rat this effect could be abolished by pretreatment with atenolol (conscious SHR), diltiazem, verapamil, propranolol and alinidine (anaesthetised rats). In addition to reflex tachycardia, BRL 38227 also increased plasma renin activity and aldosterone levels in the conscious renal hypertensive cat. In both the anaesthetised normotensive cat (0.001 mg/kg/min i.v.) and dog (0.0025 to 0.02 mg/kg i.v.) BRL 38227 lowered blood pressure and total peripheral resistance while increasing cardiac output via increased heart rate and stroke volume in the cat and via increased heart rate alone in the dog. BRL 38227 reduced renal vascular resistance in both conscious (0.01, 0.015 and 0.02 mg/kg p.o.) and anaesthetised (0.001 mg/kg/min i.v.) cats and the effect was maintained despite marked reductions in blood pressure. In the anaesthetised dog, BRL 38227 was a potent coronary arterial dilator and this effect was also maintained in the face of marked blood pressure lowering activity.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Antihypertensive and haemodynamic properties of the potassium channel activating (-) enantiomer of cromakalim in animal models. 190 50

Preservation of the donor heart is an important and controversial subject in heart transplantation. This study compares simple hypothermic storage and hypothermic perfusion in a swine model of heart transplantation (n = 14). The donor hearts of group A (n = 7) were placed in simple hypothermic storage for 5 hours. The donor hearts of group B (n = 7) were placed onto a perfusion apparatus for 5 hours, with pressure maintained at 28 cm of H2O and a myocardial temperature of 8 to 10 degrees C. In both groups the hearts were initially protected with isosmolar potassium cardioplegic solution. The perfusate in group B contained moderate sodium, mannitol, glucose, insulin, and oxygen. The ischemic interval within both groups was 6 hours including orthotopic transplantation. Investigation was conducted at three time periods: prepreservation, postpreservation, and immediately after loading. For both groups there was nonsignificant depression of myocardial function (cardiac index, stroke index, stroke work index, ejection fraction, and wall stress) at the postpreservation period. After volume loading, for the hypothermic perfusion group there was significant improvement of myocardial function (cardiac index, p less than 0.01; stroke index, p less than 0.01) with no significant change in heart rate, systemic vascular resistance, and systolic blood pressure. There was also significant improvement in myocardial performance (p less than 0.05) for the hypothermic perfusion group after volume loading. Ultrastructural changes were minimal for both groups, and there were no major heart transplantation after 6 hours of ischemia; however, hearts retain their contractile capacity better after hypothermic perfusion than after simple hypothermic storage.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Preservation techniques for heart transplantation: comparison of hypothermic storage and hypothermic perfusion. 191 94

Thirteen immature puppies (2 to 4 kg) underwent 1 hour of acute hypoxia (oxygen tension 25 to 30 mm Hg), followed by 45 minutes of normothermic global ischemia on total vented bypass with normal blood reperfusion. Ventricular function was assessed by inscribing Starling function curves and measuring stroke work indices before hypoxia and after reperfusion. Seven puppies (control) received normal saline infusion at 4 ml/kg/hr. Six other puppies received a 4 ml/kg/hr intravenous infusion of glutamate/aspartate, glucose-insulin-potassium, mercaptopropionyl glycine, carnitine, and catalase during hypoxia and reperfusion. In control hearts, acute hypoxia depleted myocardial glutamate and aspartate by 52% (p less than 0.05 versus prehypoxia) and 48% (p less than 0.05 versus prehypoxia) and caused severe hemodynamic deterioration (55% decrease of stroke work index) (p less than 0.05 versus prehypoxia); three of seven (43%) required premature institution of bypass. Postischemic left ventricular function recovered to only 40% of control levels (p less than 0.05 versus prehypoxia). In contrast, intravenous metabolic infusions maintained tissue glutamate (p less than 0.05 versus control group) and aspartate (p less than 0.05 versus control group) in treated hearts during hypoxia and allowed cardiac index to rise 20% (p less than 0.05 versus prehypoxia); all treated hearts tolerated 1 hour of hypoxia, and stroke work recovered 70% (p less than 0.05 versus control group) of stroke work index after subsequent ischemia. Impaired tolerance of immature hearts to acute hypoxia and subsequent ischemia is due to substrate depletion. This impairment can be reduced by intravenous metabolic support during hypoxia and reperfusion and leads to improved recovery of postischemic function.
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PMID:Studies of myocardial protection in the immature heart. IV. Improved tolerance of immature myocardium to hypoxia and ischemia by intravenous metabolic support. 149 25

Epidemiological evidence suggests that low potassium intake is associated with the probability of occurrence of hypertension and stroke. The short-term response to increased potassium intake is increased sodium excretion as well as increased potassium excretion; the short-term response to increased sodium intake is increased potassium excretion as well as increased sodium excretion. In some experimental studies, increased amounts of potassium have been able to block the noxious influences of sodium. Sodium and potassium must be concomitantly considered in the investigation of the association of either of these cations with hypertension and cardiovascular disease. The chloride ion is also important for sodium's effects; its importance in potassium's effects has not been extensively explored.
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PMID:Sodium-potassium interaction in hypertension and hypertensive cardiovascular disease. 198 94

Using an in vitro perfusion method, we examined the effects of cromakalim, a potassium channel opener, on the superior cerebellar arteries of 24 rats. Cromakalim had no effect on contractions induced by 129 mM K+ until a concentration of 10(-5) M was reached. Contractions evoked by 10(-5) M serotonin were attenuated by cromakalim in a concentration-dependent manner (p less than 0.05). The diameter of untreated superior cerebellar arteries remained almost constant with increasing perfusion pressure. However, in the presence of cromakalim vessel diameter increased with increasing perfusion pressure. At concentrations of 3 x 10(-6) M, cromakalim also inhibited basal myogenic tone and dilated unstimulated arteries (p less than 0.01). These results suggest that cromakalim is a cerebrovascular dilator acting on both receptor-mediated and myogenic contractions.
Stroke 1991 Feb
PMID:Cromakalim dilates rat cerebral arteries in vitro. 200 86

Major cerebral collateral arteries enlarge following bilateral ligation of the common and internal carotid arteries. The purpose of this investigation was to determine the relative contribution of cellular hypertrophy versus cellular hyperplasia to this vessel change in a morphometric analysis as well as the functional properties of remodeled vessels in an in vitro study. We assessed cell number and vessel dimensions by morphometric analysis of 16 perfusion-fixed rabbit basilar arteries. Results demonstrated significant increases in luminal diameter from 761 to 946 microns (p less than 0.01), medial cross-sectional area from 5.1 x 10(4) to 7.6 x 10(4) micron2 (p less than 0.005), smooth muscle cell volume from 9.19 x 10(5) to 1.44 x 10(6) micron3 (p less than 0.0005), and overall arterial length from 17.41 to 20.36 mm (p less than 0.005) in basilar arteries from the eight ligated rabbits compared with the eight sham-operated controls. Smooth muscle cell volume fraction and cell numerical density were unchanged whereas the number of cells per unit length of artery was increased significantly from 21.5 to 31.0 cells/micron (p less than 0.05). These data indicate that smooth muscle cell hyperplasia rather than hypertrophy contributes to increases in vessel mass. Functional properties of the basilar arteries from 10 ligated and 10 normal control rabbits were analyzed in vitro. Results showed increased contraction to potassium chloride (approximately 74%) (p less than 0.01) and increased sensitivity of smooth muscle to acetylcholine (p less than 0.05) while maximal relaxation was the same as control in the ligated animals.(ABSTRACT TRUNCATED AT 250 WORDS)
Stroke 1991 Apr
PMID:Mechanism of enlargement of major cerebral collateral arteries in rabbits. 202 79

A retrospective analysis of mortality and cardiovascular morbidity in patients being treated with a potassium losing diuretic alone or the combination of a potassium losing and sparing diuretic was performed in 1,935 patients attending a hypertension clinic between 1971 and 1981. In all, 713 patients were treated with a potassium losing diuretic and 472 patients were on a potassium sparing diuretic, usually in combination with a potassium loser. Presenting data on risk factors were similar between the two groups and age-adjusted cardiovascular morbidity and mortality was similar between the two groups. The relative risk (RR) for a myocardial infarction event on a potassium losing drug was 1.1 (95% CI 0.5-2.3) in men and 1.0 (0.4-2.5) in women. The corresponding risks for stroke were 0.8 and 0.7 respectively and total mortality was 1.3 and 1.1. However, following exclusion of patients with previous history of cardiovascular disease the risk of myocardial infarction in the potassium losing group was over three times that on a sparing diuretic, though the confidence intervals were wide. Total male mortality tended to be higher (RR = 2.4) but again failed to achieve statistical significance. An excess risk from potassium losing diuretics was found only in patients without cardiovascular disease and cannot be readily explained. This may be the result of treatment selection in different 'at risk' groups or chance in the performance of subgroup analyses.
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PMID:Myocardial infarction and stroke during treatment of hypertensive patients with different diuretic regimes. 204 Oct 35

1. The systemic and regional haemodynamic effects of the potassium channel activator EMD 52692 or its solvent were investigated after intravenous and after intracoronary administration in anaesthetized pigs. 2. Consecutive intravenous 10 min infusions of EMD 52692 (0.15, 0.30, 0.60, 1.20 micrograms kg-1 min-1; n = 7) dose-dependently decreased mean arterial blood pressure by up to 50%. This was entirely due to peripheral vasodilatation, since cardiac output did not change. Heart rate increased by up to 50%, while left ventricular end diastolic pressure decreased dose-dependently from 6 +/- 1 mmHg to 3 +/- 1 mmHg (P less than 0.05), and stroke volume decreased from 30 +/- 2 ml to 21 +/- 2 ml (P less than 0.05). Left ventricular dP/dtmax was not affected. 3. Although cardiac output did not change, EMD 52692 caused a redistribution of blood flow from the arteriovenous anastomoses to the capillary channels. Blood flow to the adrenals, small intestine, stomach, bladder, spleen and brain increased, while renal blood flow decreased and blood flow to several muscle groups and skin were not altered. Vascular conductance was increased dose-dependently in all organs, except for the kidneys, where after the initial increase, vascular conductance returned to baseline with the highest dose. Particularly striking were the effects on the vasculature of the brain. With the highest dose of EMD 52692 blood flow more than doubled, while vascular conductance increased four fold. 4. Transmural myocardial blood flow increased slightly, which was entirely due to an increase in subepicardial blood flow. Myocardial O2-consumption and segment length shortening were not significantly affected. 5. After consecutive 10 min intracoronary infusions (0.0095, 0.019, 0.0375 and 0.075 microgram kg-1 min-1; n = 7) into the left anterior descending coronary artery (LADCA), mean arterial blood pressure was maintained with the lowest two doses, but decreased by up to 15% with the higher doses, whereas heart rate increased by up to 24%. Blood flow to the LADCA-perfused myocardium doubled with the highest dose, the subepicardium benefitting the most. Coronary venous O2-saturation increased dose-dependently from 23 +/- 2% to 60 +/- 4%, while myocardial O2-consumption of the LADCA-perfused myocardium was not affected by the drug. 6. It is concluded that EMD 52692 is a potent vasodilator, with particularly pronounced effects on vasculature of the brain. Its selectivity for vascular smooth muscle cells exceeds that for the myocytes, since with doses that are much higher than those of potential clinical interest no negative inotropic effects were observed. The compound primarily dilates arteries but some venodilatation may also occur.
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PMID:Haemodynamic profile of the potassium channel activator EMD 52692 in anaesthetized pigs. 207 80

Potassium channels that are activated by decreasing adenosine trisphosphate levels are blocked by sulfonylurea drugs such as glibenclamide but are opened by diazoxide and some endogenous peptides. Judging from the effects of such drugs, it seems that in the hippocampus, these channels are present not on cell bodies but rather on glutamate-releasing nerve terminals (especially those of mossy fibers in the CA3 region). Because activation of these presynaptic potassium channels reduces anoxic glutamate release, they may be a useful target for specific drug therapy that might prevent the excitoxic effects of excessive glutamate release during anoxia/ischemia.
Stroke 1990 Nov
PMID:Adenosine triphosphate-sensitive potassium channels in anoxia. 212 55

We experienced 5 cases of acute renal failure due to rhabdomyolysis during the last two years and investigated those etiologies. Diagnosis of rhabdomyolysis was established by the detection of elevated serum creatine phosphokinase, myoglobin, aldolase, myoglobinuria as well as by the clinical course. The respective underlying illness of the 5 cases were grand mal seizures, infection (high fever), heat stroke, diabetes mellitus with hyperosmolar nonketotic coma and cerebral infarction treated by barbiturate. In this investigation, however, any single cause was not enough as the etiologies of rhabdomyolysis. There were multiple factors responsible to rhabdomyolysis in each case, such as hypokalemia, hypophosphatemia, shock, arteriosclerosis, etc. Some cases could not be classified as traumatic or non-traumatic rhabdomyolysis. Thus, in one case, acute renal failure due to rhabdomyolysis induced by the combination of grand mal seizures and serum potassium/phosphate depletion. 2 cases recovered without hemodialysis. 3 cases died in multiple organ failure, included a case treated by hemodialysis. We conclude that acute renal failure due to rhabdomyolysis induced easily by numerous diseases and early diagnosis is recommended.
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PMID:[Investigation of etiologies for acute renal failure due to rhabdomyolysis in 5 patients]. 212 50


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