digoxin and Ischemia

Therapeutic angiogenesis is a potential therapeutic strategy for hind limb ischemia (HLI); however, currently, there are no small-molecule drugs capable of inducing it at the clinical level. Activating the hypoxia-inducible factor-1 (HIF-1) pathway in skeletal muscle induces the secretion of angiogenic factors and thus is an attractive therapeutic angiogenesis strategy. Using salidroside, a natural glycosidic compound as a lead, we performed a structure-activity relationship (SAR) study for developing a more effective and druggable angiogenesis agent. We found a novel glycoside scaffold compound (

Topics: Angiogenesis Inducing Agents; Animals; Diabetes Mellitus, Experimental; Glucosides; Glycosides; Hindlimb; Ischemia; Male; Mice; Mice, Inbred C57BL; Neovascularization, Pathologic; Phenols; Rats; Rats, Sprague-Dawley

Topics: Adult; Apocynaceae; Atrial Fibrillation; Colectomy; Digoxin; Electrocardiography; Extracorporeal Membrane Oxygenation; Fruit; Humans; Immunoglobulin Fab Fragments; Intestines; Ischemia; Life Support Care; Male; Ventricular Fibrillation

Topics: Aged; Cardiotonic Agents; Diagnosis, Differential; Digoxin; Heart Failure; Humans; Ischemia; Male; Mesentery; Time Factors; Ultrasonography, Doppler

Two patients with atrial fibrillation had abrupt onset of abdominal pain and massive small bowel distension suggesting mesenterial artery embolism. One patient had dilation of the left atrium and ventricle, the other a mitral value prolapse syndrome with a dilated left atrium. Both patients were treated conservatively and gradually recovered. A small bowel series performed several weeks after the acute episode showed loss of normal mucosa and narrowing of a long segment of the small bowel. A control examination in one patient one year later, still revealed jejunal mucosal abnormalities and stenosis, features similar to those occurring in Crohn's disease. Our observations suggest that analogous to ischemic colitis, an entity of acute ischemic small bowel enteritis exists. Mesenteric ischemia apparently can induce a clinical syndrome of "regional enteritis". The radiologic features should not be confused with those of Crohn's disease.

Topics: Aged; Anticoagulants; Digoxin; Heart Diseases; Humans; Intestinal Obstruction; Intestine, Small; Ischemia; Male; Mesenteric Arteries; Mesenteric Vascular Occlusion; Radiography; Thrombosis

To characterize any digitalis-induced differences in intestinal blood flow autoregulation, we studied the circulatory responses of the rat intestine in control (n = 7) and chronically digitalized (n = 7) animals. Data were generated from denervated isoperfused small intestinal preparations. Arterial pressure, venous pressure, and oxygen consumption were continuously monitored. Determinations of intestinal blood flow allowed calculation of mesenteric vascular resistance and oxygen consumption. Animals underwent stepwise reductions in arterial pressure and acute venous hypertension (10 to 15 mm Hg). There were no differences in baseline hemodynamic or metabolic parameters in control (C) or digitalized (D) animals. Blood flow and oxygen consumption were autoregulated in both C and D rats until perfusion pressure decreased below 50 mm Hg. The response to acute venous hypertension was different. In D rats, venous hypertension resulted in increased vascular resistance (millimeters of mercury per milliliter per minute per 100 gm) [0.89 +/- 0.05 to 0.97 +/- 0.07; p less than 0.05], whereas C rats demonstrated no change [0.92 +/- 0.08 to 0.95 +/- 0.09]. The decrease in oxygen consumption in D rats (-14%) was slightly but significantly greater than that observed in C rats (-9%). Digitalized rats demonstrated a heightened myogenic response to acute venous hypertension with deleterious effects on vascular resistance and oxygen consumption. This reaction was intrinsic to the mesenteric circulation and not mediated by sympathetic nerves or central reflexes. Nonocclusive mesenteric ischemia in digitalized patients may reflect a similar abnormal response to the acute increases in portal pressure accompanying cardiac failure.

Topics: Animals; Blood Pressure; Digitalis; Digoxin; Homeostasis; Humans; Intestine, Small; Ischemia; Male; Mesenteric Arteries; Mesenteric Veins; Oxygen Consumption; Plants, Medicinal; Plants, Toxic; Rats; Rats, Inbred Strains; Splanchnic Circulation; Time Factors; Vascular Resistance

Three structurally related peptides, ovine corticotropin-releasing factor, sauvagine, and urotensin I are selective mesenteric vasodilators in dogs. To assess the possible benefit of these peptides in nonocclusive mesenteric ischemia, they were compared with a nonselective vasodilator, sodium nitroprusside, in the anesthetized dog. Mesenteric blood flow was reduced by approximately 30%, without lowering of systemic arterial pressure, by either digoxin or pericardial tamponade. In the digoxin model, i.v. infusions of corticotropin-releasing factor, sauvagine, and urotensin I restored intestinal vascular resistance and mesenteric blood flow to control values, without causing a fall in systemic arterial blood pressure. In the tamponade model, only urotensin I was assessed, and it produced the same restoration of hemodynamic variables. On the other hand, in both models, i.v. infusions of nitroprusside, which were effective in correcting intestinal vascular resistance, produced a fall in arterial blood pressure (presumably because of systemic dilatation), which prevented restoration of mesenteric blood flow. Intestinal oxygen uptake was not altered by tamponade, but was reduced by 23% in the digoxin model, where it was restored to control values by both the peptides and nitroprusside. The increased oxygen extraction seen in both models was corrected by the peptides but not by nitroprusside, suggesting that nitroprusside may have a direct and offsetting metabolic effect on the gut.

Topics: Amphibian Proteins; Animals; Blood Pressure; Cardiac Tamponade; Corticotropin-Releasing Hormone; Digoxin; Diuresis; Dogs; Female; Ischemia; Male; Mesenteric Arteries; Mesenteric Veins; Nitroprusside; Peptide Hormones; Peptides; Splanchnic Circulation; Urotensins; Vascular Resistance; Vasodilator Agents

Topics: Abdomen, Acute; Adult; Anti-Anxiety Agents; Bromazepam; Colitis; Colon; Digoxin; Female; Humans; Ischemia; Isosorbide Dinitrate; Radiography; Suicide, Attempted; Tablets

Topics: Animals; Digoxin; Dogs; Drug Evaluation, Preclinical; Hemodynamics; Ischemia; Peritoneal Diseases; Splanchnic Circulation; Vasodilator Agents

Topics: Animals; Digoxin; Dogs; Female; Glucagon; Hemodynamics; Histamine; Ileum; Ischemia; Jejunum; Male; Mesenteric Arteries; Perhexiline; Piperidines

It is the bicentennial anniversary of the introduction of digitalis into medicine. Digitalis is one of the most important drugs ever discovered, and after two centuries, it is still the most widely used drug in cardiology. However, it was at one time so badly abused that for nearly a century it was almost abandoned. Early in this century, the valuable effects of digitalis were once again recognized and extended. The molecular basis of action has been defined and now methods are available to detect early toxicity. Recent advances in combating toxic effects show considerable promise. Skillful administration of the drug, using purified standard tablets, careful monitoring by clinical electrocargiography, and analytical methods can secure the maximun benefits with the minimum degree of toxicity.

Topics: Arrhythmias, Cardiac; Digitalis Glycosides; Digitoxin; Digoxin; England; Heart; Heart Failure; History, 18th Century; Humans; Intestinal Absorption; Intestines; Ischemia; Pacemaker, Artificial; Suicide; Tablets; Time Factors

Previous studies have been shown that intravenous cardiac glycosides produce mesenteric vasoconstriction (MVC). The possibility that this might critically compromise blood flow in patients with mesenteric vascular disease was suggested. To evaluate whether MVC occurs with intravenous cardiac glycosides in the presence of proximal mesenteric artery stenosis, blood flow in the superior mesenteric artery (SMA) of thirteen dogs was measured with a Doppler flowmeter. The SMA was constricted and pressures were measured in the aorta, SMA, and superior mesenteric vein. Superior mesenteric vascular resistance (SMVR) was calculated by dividing the pressure difference between the SMA and superior mesenteric vein by the total blood flow to the superior mesenteric vasculature and was reported as mm Hg/cc-min. Blood flow was measured simultaneously by a drop rate meter in the vein of a surgically isolated intestinal segment supplied by a single arterial arcade. Venous outflow pressure from this segment was also monitored, which allowed calculation of isolated gut segment resistance (IGSR) in mm Hg/cc-min per 100 g gut. Stenosis of the SMA produced pressure gradients of 10 to 75 mm Hg and decreased resting blood flow by as much as 82%. Digoxin produced an increase in both SMVR and IGSR throughout the 30 to 120 minute period of the study in thirteen dogs despite the presence of severe grades of SMA stenosis. There was no relationship between the degree of proximal SMA stenosis and the magnitude of resistance change due to digoxin. To determine if this MVC was reversible, glucagon was administered to eleven dogs 30 to 60 minutes after digoxin and completely overcame the constriction. Thus, digoxin produced MVC in the presence of proximal SMA stenosis. This MVC was pharmacologically reversible. These data suggest that intravenous digoxin might contribute to intestinal ischemia in patients with preexisting vascular disease.

Topics: Animals; Blood Pressure; Digoxin; Dogs; Glucagon; Haplorhini; Homeostasis; Humans; Intestines; Ischemia; Mesenteric Arteries; Mesenteric Vascular Occlusion; Mesenteric Veins; Regional Blood Flow; Vascular Resistance

Nonocclusive mesenteric ischemia was produced in dogs by intraarterial infusion of digoxin and by hemorrhage of 1/3 of total blood volume. Both methods produced a substantial drop in the superior mesenteric arterial blood flow rate. In each case, a superior mesenteric arterial infusion of 0.1 mug./kg. per minute of prostaglandin E1 allowed the blood flow rate to increase to above the control level without significantly altering heart rate or systemic arterial pressure. The improved arterial blood flow rates were accompanied by a reversal of the diffuse mesenteric vasoconstriction that was seen in the ischemic state. These findings were demonstrated by superior mesenteric arteriography performed prior to and following the production of mesenteric ischemia and again following the infusion of prostaglandin E1.

Topics: Animals; Digoxin; Disease Models, Animal; Dogs; Ischemia; Mesenteric Arteries; Mesentery; Prostaglandins E; Radiography

Topics: Adrenergic beta-Antagonists; Animals; Coronary Vessels; Digoxin; Dipyridamole; Dogs; Heart; Ischemia; Isoproterenol; Microcirculation; Nitroglycerin; Papaverine

Topics: Acute Disease; Animals; Blood Pressure; Chronic Disease; Coronary Circulation; Coronary Vessels; Digoxin; Dogs; Electrocardiography; Electrodes; Heart Ventricles; Ischemia; Ligation; Myocardial Infarction; Time Factors; Tritium

Topics: Bile Acids and Salts; Cerebrovascular Disorders; Digoxin; Drug Synergism; Humans; Ischemia; Magnesium; Nicotinic Acids

Topics: Adult; Aged; Animals; Cardiomyopathies; Cardiovascular Diseases; Cats; Digoxin; Female; Heart Valve Diseases; Humans; Ischemia; Male; Middle Aged; Potassium Deficiency; Pulmonary Heart Disease