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Biomedical subjects

M J Zinner

Publications and source records attributed to M J Zinner.

At least 127 records · Page 7Linked to original sources

Microvascular architecture of anthropoid primate intestine.

Microvascular architecture of the small intestine of New World monkey, ape, and man was examined with the silicone rubber injection technique and the results compared to previous observations in dogs and Old World monkeys. In man, chimpanzee, and New World monkey the small intestine villus contains a single centrally located vein draining a subepithelial capillary plexus converging at the apex of the villus. These villi also contain a single eccentrically located artery rising to the midlevel of the villus, where it branches into subepithelial capillaries over the rest of its length. This vascular architecture most closely resembles that observed in the gut of Old World monkeys in which the villus artery is absent altogether. This observation contrasts the microvascular architecture of canine intestinal villi in which marginal arteries surround a centrally located vein. These patterns of microvascular anatomy are analyzed in terms of the role of the gut in the pathogenesis of experimental shock. The differences observed may account for the known species variations in canine and primate experimental shock.

Adult↗

Regional gastric blood flow in cynomolgus monkeys with hemorrhagic shock and resuscitation.

Five anesthetized cynomolgus monkeys were subjected to hemorrhagic shock (42 +/- 3 mm Hg) for four hours and then resuscitated with shed blood and intravenous fluids to restore mean arterial pressure and arterial pH to control levels. Regional gastric blood flow was measured by radioactive microspheres. Responses were similar in all regions, except mucosal blood flow increased significantly (from 20.1 +/- 5.1 to 42.1 +/- 7.6 ml/min 100 gm of tissue) in response to resuscitation in the antrum but not in the fundus or corpus. This difference in response may explain the occurrence of stress ulcers in the proximal stomach with sparing of the antrum.

Animals↗

Vasodilation, fibrinolysis, and thrombolysis with intraarterial infusion of urokinase in the canine superior mesenteric artery.

Urokinase, the plasminogen activator from human urine, produces a dose-dependent increase in blood flow in the canine superior mesenteric artery when injected intraarterially at doses from 10(-1) to 10(3) units kg-1. This vasodilation persists despite blockade of beta-adrenergic and histamine H1 and H2 receptors as well as inhibition of plasminogen activation, suggesting that these mechanisms are not involved. Infusion of urokinase at 10(2) CTA (Committee on Thrombolytic Agents) units kg-1 min-1 does not produce a sustained vasodilation, but is effective in achieving complete lysis of thrombi within 100 min in the superior mesenteric arterial circulation. Increasing the dose slightly to 125 CTA units kg-1 min-1 results in unwanted clotting abnormalities without attaining a vasodilator level. Decreasing the dose to 75 CTA units kg-1 min-1 still results in complete thrombolysis. In contrast to the results in the femoral circulation, the dose required for fibrinolysis-thrombolysis does not overlap with that for vasodilation in the superior mesenteric artery. Nevertheless, these experiments provide some basis for the use of intraarterial urokinase infusion in the treatment of nonocclusive mesenteric ischemia and, perhaps, thrombotic occlusion of the superior mesenteric artery.

Animals↗

The effect of hemorrhagic shock and resuscitation on regional blood flow in cynomulgus monkeys.

The effect of hemorrhagic hypotension and resuscitation on regional blood flow was studied in the Macaca fascicularis monkey. The majority of the splanchnic vasculature demonstrated a profound decrease in flow. Following fluid expansion and correction of acidosis, flow increased in these circulations but did not reach control values. Exceptions were the small bowel flow which fell only moderately and hepatic arterial flow which did not significantly change. Both coronary and adrenal circulations maintained flow during the shock and resuscitation periods, whereas brain and kidney blood flows fell significantly without recovery. There was a significant rise in serum glucose, lactate, and pyruvate during shock, with an increase in the lactate/pyruvate ratio. Following resuscitation, the ratio decreased, implying a return toward aerobic metabolism.

Animals↗

Vasodilation due to urokinase in the canine femoral circulation.

Based upon clinical observations, we hypothesize that the plasminogen activator urokinase is vasoactive in addition to being fibrinolytic and thrombolytic. The effects of intra-arterial injections and infusions of urokinase were investigated in the canine femoral circulation. Injections of human urine urokinase increased femoral artery blood flow in a dose-related fashion that was not significantly attenuated by beta adrenergic blockade, antihistamine treatment, heating, atropine treatment or kallikrein inactivation. The Ploug preparation of urine urokinase was somewhat more effective than the Abbott or Sterling-Winthrop preparations in causing this dilation. Some nonspecific inhibition of the vasodilator responses was produced by inhibition of plasminogen activation with epsilon-aminocaproic acid. The continuous infusion of urokinase increased femoral arterial flow but there was some tendency to escape. Further experiments seem indicated to determine potential application of local urokinase in clinical conditions where vasodilation and fibrinolysis-thrombolysis might be of value.

Animals↗

Effect of histamine H2 antagonism by metiamide on the response of the canine gastric mucosa to acid and bile salt.

Prevention of acute gastric erosions with histamine H2-receptor blocking agents suggests that these drugs may improve the ability of the gastric mucosa to maintain electrical, ionic, and protein concentration gradients. In 5 awake mongrel dogs, transmural potential difference, ion fluxes, and protein loss were measured across Heidenhain pouches topically exposed to isotonic solutions containing either 80 mM HCl or 80 mM HCl plus 20 mM sodium taurocholate (BS). The dogs received an intravenous infusion of either saline (as a control) or the H2 antagonist metiamide, 10 mumoles per kg-hr. Metiamide increased the H+ clearance rate found after acid test solution exposure but had no significant effect on potential difference or ion fluxes. H2 antagonism decreased the protein loss but not the increase in cation permeability due to BS. Net H+ loss actually increased, which, along with a decrease in Cl- gain, suggests inhibition of acid secretion by metiamide in BS-exposed gastric mucosa. These effects of metiamide point to histamine as a likely mediator of the gastric mucosal damage due to BS.

Animals↗

Septic nonsuppurative thrombophlebitis.

Nonsuppurative peripheral thrombophlebitis is a frequently recognized source of sepsis. Eleven patients cared for on general medical and surgical services had Gram-negative bacillary sepsis on this basis. Ten had isolation of organisms of the Klebsiella-Enterobacter group from the involved peripheral vein. All failed to respond to organism-sensitive antibiotics until the involved vein was excised. After local vein excision, all patients were afebrile within 48 hours and recovered. In seven of the 11 patients, the septic phlebitis source was associated with a standard intravenous needle, and none had cutdown procedures. It is strongly emphasized that this condition is a source of life-threatening sepsis that can be treated by vein excision at the bedside. The treatment in our patients resulted in no morbidity. A high index of suspicion is necessary to diagnose this occult source of sepsis because of the minimal local physical signs.

Adult↗

Primate gastric circulation: effects of catecholamines and adrenergic blockade.

The effects of intra-arterial injections and infusions of epinephrine, norepinephrine, and isoproterenol on gastric blood flow were studied in anesthetized baboons. Blood flow was measured electromagnetically before and after adrenergic blockade. The results for injected epinephrine and norepinephrine indicate these agents to be pure vasoconstrictors in the primate gastric circulation, and this response is attenuated by alpha-adrenergic blockade with phenoxybenzamine. Isoproterenol is a pure vasodilator, and its response is attenuated following beta-adrenergic blockade with propranolol. Intra-arterial infusions of epinephrine and norepinephrine (.05 mug kg-1 min-1) resulted in sustained vasoconstriction with no evidence of autoregulatory escape and no postinfusion "over-shoot." This study suggests that epinephrine and norepinephrine might provide alternatives to vasopressin as a vasoconstrictor for the control of upper gastrointestinal bleeding.

Animals↗

Cerebral blood flow determinations by radioactive microspheres in the subhuman primate: influence of unilateral internal carotid ligation, hypercapnic acidosis, and hypocapnic alkalosis.

Cerebral blood flow (CBF) was measured by electromagnetic and radioactive microsphere (RMS) techniques in the anubis baboon. Regional cerebral blood flows were calculated by distribution of intracardiac injections of RMS, labeled with one of three radionuclides: 51Cr, 85Sr, or 141Ce. In Group I (six animals, normocapnia), CBF's as estimated by electromagnetic measurement of internal carotid blood flow, were 65 +/- 10 and 74 +/- 4 (S.E.M.) ml. per minute per 100 Gm. for the right (RH) and left (LH) cerebral hemispheres, respectively; whereas CBF's as estimated by the RMS technique were 65 +/- 5 and 70 +/- 4 ml. per minute per 100 Gm., respectively, and these values were not significantly (p greater than 0.05) different. CBF, as determined by RMS techniques in Group 1, was not altered by unilateral internal carotid arterial ligation. In Group 2 (seven animals), arterial PCO2 was varied randomly from a low range (18 +/- 2 mm. Hg, L), to a middle range (PCO2 36 +/- 2, M), and a high range (PCO2 64 +/- 2, H), and CBF was measured by the RMS technique. During L, M, and H, CBF's were 44 +/- 10, 75 +/- 15, and 159 +/- 27 ml. per minute per 100 Gm., respectively, for RH, whereas CBF's were 44 +/- 10, 75 +/- 15, and 160 +/- 26 ml. per minute per 100 Gm., respectively, for LH. During H, RH and LH were significantly (p less than 0.05) greater than during L and M. Changes in regional CBF were uniform throughout the brain. These data demonstrate the correlation between CBF, as estimated by electromagnetic and RMS techniques, as well as confirm the adequacy of collateral cerebral circulation during unilateral carotid arterial ligation in the baboon. The usefulness of the RMS technique for hemispheric and regional CBF measurements is prevented also.

Acidosis, Respiratory↗

Distribution and arteriovenous shunting of gastric blood flow in the baboon: effect of epinephrine and vasopressin infusions.

The effects of 60-min intraarterial infusion of vasopressin (0.005 U per kg-min) and epinephrine (0.05 mu per kg-min) on gastric hemodynamics were studied in anesthetized baboons. Total gastric blood flow was measured electromagnetically and radioactive microspheres (15 +/- 5 mu) with three labels were used to determine regional distribution of gastric blood flow and arteriovenous shunting. Control flow was 55 +/- 8 ml per min, with 77.4 +/- 2.7% of flow going to the gastric mucosa and 1.7 +/- 0.4% of injected spheres appearing in the liver. Epinephrine infusion resulted in a sustained vasoconstriction to 18 +/- 5 ml per min with no autoregulatory escape and no changes in arterial pressure or cardiac output. Vasopressin resulted in a decrease in flow to 14 +/- 3 ml per min with no excape. Whereas cardiac output did not change, there was a singificant hypertensive effect during the vasopressin infusion. There was neither redistribution of flow nor change in arteriovenous shunting with either epinephrine or vasopressin. Transmucosal electrical potential difference was 62 +/- 8 mv and did not change significantly with either infusion.

Animals↗

Adrenergic mechanisms in canine gastric circulation.

The effects of adrenergic stimulation and blockade on the gastric circulation were studied in anesthetized dogs. Blood flow through the right and left gastric artery was measured electromagnetically. Norepinephrine and isoproterenol were injected intra-arterially and intravenously before and after alpha- and beta-adrenergic blockade. Isoproterenol caused vasodilation of both right and left gastric circulations and this effect was attenuated by beta blockade. Epinephrine and norepinephrine induced constriction followed by dilation in both circulations. The constrictor components were attenuated or abolished by alpha-adrenergic blockade and the dilator components were attenuated by beta-adrenergic blockade. The right and left gastric vascular beds demonstrated quantitatively different responses to the same dose of each adrenergic amine. The left gastric circulation had a greater vasodilator response than did the right gastric circulation. These data support the classical concepts that epinephrine and norepinephrine are "mixed" adrenergic agonists and isoproterenol is a "pure" beta-adrenerigic agonist. The data further suggest that there is a differential in beta-adrenergic receptor distribution with the left gastric vasculature demonstrating greater dilator responses than the right.

Adrenergic Agonists↗

Stress ulceration and the gastric mucosal barrier.

The role of the gastric mucosal barrier in the pathogenesis of post-traumatic stress ulcerations is far from clear. Clinical studies on critically ill patients have shown disrupted gastric mucosal barriers with hydrogen ion back diffusion, but no correlation has been made between these findings and gastric erosions. In addition, numerous assumptions concerning gastric secretions, pyloric loss and esophageal contributions to the assayed gastric juice have to be made in these patients. There is contradictory experimental evidence concerning the theory that gastric mucosal ischemia or hypotension disrupts the normal gastric mucosal barrier. In subhuman primate studies, there is no increased back diffusion acid during hypotension or during the reinfusion periods. Even though there may not be increased permeability to H+, the presence of acid is a requirement for the development of stress ulcerations. The role of agents such as bile salts and aspirin is clearer. If these agents are present, increased back diffusion of acid is likely, but its role in the pathophysiology of post-traumatic gastric erosion awaits further clarification.

Animals↗

The role of acid and ischemia in production of stress ulcers during canine hemorrhagic shock.

Hemorrhage to a mean arterial pressure of 41 mm. Hg in ten dogs decreased Heidenhain pouch blood flow to 6 ml. per minute and aminopyrine clearance to 0.93 ml. per minute. Pouch oxygen consumption fell from 1.47 to 0.74 ml./min.-100 Gm. and total body oxygen consumption remained unchanged. Net ion fluxes during shock and reinfusion did not change significantly from control values of minus 89.8 muGq./30 min.-100 cm.-2 for H-+ and 88.6 muEq./30 min.-100 cm-2 for Na-+. However, PD decreased from 54 to 24 mv. in parallel with a fall in net Cl-minus flux from 56.8 to minus 11.7 muEq./30 min.-100 cm-2. Nine of ten pouches subjected to shock and instilled acid test solution (ATS) developed superficial mucosal erosions. No ulcerations were found in either seven control dogs (anesthesia + ATS) or in three dogs subjected to shock without ATS. Acid appears to be of prime importance in the production of stress ulcers during or following ischemia, even though there is no increase in mucosal ionic permeability.

Acids↗