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Y S Sun

Publications and source records attributed to Y S Sun.

31 records · Page 2Linked to original sources

Selective neurohormonal interactions in islet cell secretion in the isolated perfused human pancreas.

To investigate the effects of stimulant interactions on alpha- and beta-cell secretions, the differential effects of gastric inhibitory polypeptide (GIP) and cholinergic stimulation (CS) on insulin (IRI) and glucagon (IRG) release were examined during euglycemic, single-pass perfusion in the isolated human pancreas. Pancreata obtained from 12 cadaver organ donors were perfused for 15-min test periods with (a) 1 nM GIP (b) intrinsic CS via bipolar electrical stimulation (10 V, 5 msec, 10 Hz) of the splanchnic neural fibers during simultaneous perfusion with 4 microM phentolamine and 6 microM propranolol, or (c) GIP and CS. The integrated response of IRI and IRG demonstrated that IRI release was stimulated 308 +/- 52 microU/g-min by GIP, 366 +/- 73 microU/g-min by CS, and 560 +/- 50 microU/g-min by GIP and CS (P less than 0.05). IRG release was stimulated 111 +/- 33 pg/g-min by GIP, 34 +/- 12 pg/g-min by CS, and 90 +/- 36 pg/g-min by GIP and CS. Combined hormonal and cholinergic stimulation was additive for IRI release, but not for IRG release. We conclude that the interaction of neural and hormonal islet cell stimuli is cell-type specific. This may result in selective impairment of hormone release after pancreatic denervation.

Adolescent↗

Transfemoral balloon aortic occlusion during open cardiopulmonary resuscitation improves myocardial and cerebral blood flow.

These experiments were designed to determine whether the limited cardiac output during open cardiac massage could be preferentially directed to the coronary and cerebral vessels by balloon occlusion of the descending thoracic aorta. Sixteen dogs were instrumented to monitor cardiac output and left atrial, right atrial, right ventricular, left ventricular, and arterial blood pressures. Measurements of myocardial and cerebral blood flow distribution during massage were made using the radioactive microsphere technique. Each animal underwent two episodes of fibrillation and resuscitation. In one episode the arrest was managed by open massage alone, and in the other, open massage was accompanied by balloon occlusion, with the order randomized. When compared to control, open cardiac massage was associated with a significant decrease in mean arterial pressure; however, the addition of balloon occlusion produced a 130% increase in the mean arterial pressure that was obtained during open CPR (control, 93 +/- 5 mm Hg; massage alone, 35 +/- 2 mm Hg; massage + balloon, 76 +/- 2 mm Hg, P less than 0.01). In a similar fashion, although the absolute blood flow was reduced by 50% when compared to control, the blood flow (ml/min/g) to the brain and heart during massage was 100% better when balloon occlusion was employed (brain: control, 0.41 +/- 0.03; massage only, 0.05 +/- 0.01; massage + balloon, 0.25 +/- 0.02, P less than 0.01; heart: control, 1.46 +/- 0.11; massage alone, 0.35 +/- 0.05; massage + balloon, 0.71 +/- 0.05, P less than 0.01). These results suggest that aortic occlusion significantly increased myocardial and cerebral perfusion patterns during ventricular fibrillation and open cardiac massage.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Reappraisal of the mechanism for cerebrospinal fluid hypertension during aortic surgery.

Cerebrospinal fluid (CSF) hypertension during aortic surgery is a poorly understood, multifactorial event that may increase the risk of spinal cord injury. To assess the factors that may contribute to changes in CSF pressure during aortic surgery, measurements of ascending arterial and CSF pressures were made in 17 anesthetized mongrel dogs. Changes in CSF patterns were monitored under several conditions tested in random sequence. These included systemic hypertension produced by an infusion of phenylephrine, cross-clamping of the descending thoracic aorta, and manual, superior displacement of the transverse aortic arch (arch elevation), either alone or in conjunction with the cross-clamp. Hypertension, cross-clamping, and cross-clamping combined with arch elevation all produced significant increases in ascending mean arterial pressure (204 +/- 20, 170 +/- 8, and 158 +/- 11 mm Hg, respectively, vs. 117 +/- 8 mm Hg [control]; (p less than 0.01). Small, nonsignificant increases in CSF pressure were detected in the cross-clamp group, but none were detected with hypertension alone, despite significant increases in ascending arterial blood pressure in both groups. Thus, neither arterial hypertension nor cross-clamping alone could be demonstrated directly to cause significant CSF hypertension. However, when aortic elevation (displacement) was combined with cross-clamping, the rise in CSF pressure increased to significant levels, even though the ascending arterial hypertension was least severe in this group. In contrast, arch elevation alone did not produce any significant increase in ascending arterial pressure but did produce an approximately 114% increase in CSF pressure (15.2 +/- mm Hg vs. 7.7 +/- 1 mm Hg [control]; p less than 0.01.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Improvement in thoracic aortic pressure after proximal aortic cross-clamping by balloon occlusion of the distal aorta.

Spinal cord hypoperfusion injury is a devastating complication of cross-clamping the proximal thoracic aorta. The collateral circulation around the cross-clamp is generally poorly developed, and the run-off is immense, resulting in extremely low thoracic aortic and spinal cord perfusion pressures. The authors postulated that balloon occlusion of the abdominal aorta might confine this reduced collateral flow around the cross-clamp to the thoracic aorta. In 8 of 16 dogs subjected to aortic cross-clamping of the aorta just beyond the arch vessels, the abdominal aorta was also occluded by a balloon. Thoracic aortic pressure and spinal cord perfusion pressure were significantly higher in the animals with aortic balloon occlusion than in those without balloon occlusion (77 +/- 8 mm Hg versus 26 +/- 1 mm Hg, p less than 0.01, and 67 +/- 8 mm Hg versus 18 +/- 2 mm Hg, p less than 0.01, at 10 minutes after cross-clamping). Abdominal aortic balloon occlusion increases thoracic aortic pressure after the aorta is cross-clamped proximally. Further studies are necessary in primates to assess the effect of this procedure in spinal cord perfusion and the rate of paraplegia.

Animals↗

Splanchnic neural regulation of pancreatic polypeptide release in the isolated perfused human pancreas.

The isolated perfused human pancreas was employed as a model in which electrical stimulation of the celiac mixed neural bundle was performed in the presence and absence of selective neural antagonists. Stimulation of the celiac neural bundle in the presence of hyperglycemia resulted in augmentation of pancreatic polypeptide release. Cholinergic stimulation appears to predominate, whereas beta-adrenergic fibers stimulate pancreatic polypeptide-cell secretion, and alpha-adrenergic fibers inhibit pancreatic polypeptide release. During euglycemia, both cholinergic stimulation and gastric inhibitory polypeptide infusion resulted in a marked release of pancreatic polypeptide. These stimulatory effects were additive, which suggests a linked hormonal and neural mechanism of pancreatic polypeptide release after a meal. In this in vitro human model, our data confirm that the splanchnic innervation of the pancreas has a potent regulatory role in pancreatic hormone release in man.

Adolescent↗

Regulation of pancreatic polypeptide secretion in the isolated perfused human pancreas.

The isolated perfused human pancreas was used as a model to assess factors mediating the pancreatic polypeptide cell response to glucose, insulin, gastric inhibitory polypeptide, and splanchnic nerve stimulation. Pancreases obtained from 18 cadaveric organ donors were isolated and perfused by way of the splenic artery utilizing a Krebs bicarbonate buffer in a single-pass perfusion system. Hormonal stimulation and inhibition of pancreatic polypeptide secretion were assessed, as was the influence of direct electrical stimulation of celiac neural fibers innervating the pancreas. In this in vitro human model, pancreatic polypeptide cell secretion was inhibited by hyperglycemia, although the presence of gastric inhibitory polypeptide augmented the pancreatic polypeptide cell response. Perfusion with low levels of insulin and splanchnic nerve stimulation augmented the response of the pancreatic polypeptide cell to hyperglycemia and gastric inhibitory polypeptide. Since the immunoreactive pancreatic polypeptide response was augmented when insulin and somatostatin release was inhibited by perfusion insulin or nerve stimulation, we conclude that the pancreatic polypeptide cell is regulated by the ambient degree of somatostatin release, insulin release, or both. These findings support a centrifugal pattern of intraislet blood flow.

Adolescent↗

Splanchnic neural regulation of insulin and glucagon secretion in the isolated perfused human pancreas.

The isolated perfused human pancreas was employed as a model in which electrical stimulation of the celiac mixed neural bundle was performed in the presence or absence of selective neural blockers. The insulin and glucagon responses to hyperglycemia alone or in the presence of splanchnic nerve stimulation were similar in magnitude to the results obtained in a preliminary report on isolated human pancreatic function and in studies using animal models. Stimulation of the celiac neural bundle in the presence of hyperglycemia resulted in an inhibition of insulin release and in an augmentation of glucagon release. alpha-adrenergic stimulation resulted in a strong suppression of insulin secretion and a mild suppression of glucagon secretion. beta-adrenergic fiber stimulation caused a mild augmentation of both insulin and glucagon release, whereas the cholinergic fibers strongly stimulated both alpha- and beta-cell secretion. The predominant effects of celiac neural bundle stimulation are insulin inhibition by was of an alpha-adrenergic effect and glucagon stimulation by way of a cholinergic effect. Thus, in this in vitro human model, our data confirm that the splanchnic innervation of the pancreas has a potent regulatory role on pancreatic hormone release in human subjects.

Adolescent↗

Reversal of abnormal glucose metabolism in chronic pancreatitis by administration of pancreatic polypeptide.

Chronic pancreatitis, induced in dogs by pancreatic duct ligation, is associated with glucose intolerance due to insulin deficiency, reduced hepatic sensitivity to insulin, and a marked deficiency of pancreatic polypeptide. Treatment with a 14 day continuous subcutaneous infusion of pancreatic polypeptide resulted in improved oral glucose tolerance and improved hepatic glucose responses to insulin in dogs with chronic pancreatitis. No effect of continuous subcutaneous infusion of pancreatic polypeptide was seen in the control dogs. The time course of the effect of continuous subcutaneous infusion on the hepatic response to insulin was relatively immediate, whereas the effects on improvement in oral glucose tolerance were prolonged. We conclude that pancreatic polypeptide may function physiologically to enhance the hepatic glucose response to insulin and that alterations in glucose metabolism seen in chronic pancreatitis may be due, in part, to a deficiency in pancreatic polypeptide. Since treatment with continuous subcutaneous infusion of pancreatic polypeptide restored the hepatic response to insulin and oral glucose tolerance to more normal levels in our animal model, administration of pancreatic polypeptide may play a therapeutic role in the treatment of certain forms of pancreatogenic diabetes.

Animals↗

A carotid stenosis model in canines.

A carotid stenosis model was developed in canines in order to study the effects of systemic blood pressure and hemodilution on cerebrovascular perfusion and metabolism during cardiopulmonary bypass in the setting of significant coexistent inflow stenosis. Under general anesthesia, through a low midline neck incision, the carotid sheath was entered and the carotid artery was isolated and retracted medially. The vertebral artery could be identified posterolaterally. After ligating the vertebral artery with a 00 silk tie, carotid stenosis was created by tying bilateral carotid arteries over an 18-gauge needle using a 00 silk tie. The needle was then removed, leaving a tight stenosis. To determine the degree of stenosis, arteriograms were performed, revealing high-grade lesions of greater than 90% stenosis in the carotid arteries and absence of flow through the vertebral arteries. Cerebral blood flow studies during cardiopulmonary bypass (CPB) were performed, revealing a significant decline. Carotid arteries were harvested at the conclusion of the experiments, revealing tight lesions on direct inspection. The mean gradient measured across stenotic segments was >25 mm Hg. In conclusion, a carotid stenosis model can be created successfully in dogs by ligating the vertebral arteries bilaterally and simply using the shaft of a needle to standardize the lumen size of the carotid arteries. We found the diameter of an 18-gauge needle sufficient to produce stenoses of greater than 90% as evidenced by arteriograms.

Animals↗

Cardiac pacing induced flow responses in internal thoracic artery and saphenous vein coronary artery bypass grafts.

The flow reactivity of an internal thoracic artery (ITA) graft and a vein graft for multiple coronary beds in response to different modes of cardiac pacing remains unclear. These experiments were conducted in 14 anesthetized dogs with the ITA or the vein grafted to the circumflex coronary artery, off pump, using a brief local occlusion. The left main coronary artery was occluded, rendering the entire left ventricle totally dependent upon the ITA graft or the vein graft. When the left main coronary artery was occluded and the heart rate was 120 beats per min, graft flow was 93.4 +/- 9.6 ml per min in the ITA, and 96.1 +/- 10.4 ml per min in the vein graft. Atrial pacing to increase heart rates 25% to 150 beats per min increased both the ITA graft flow (110.3 +/- 9.7 ml per min, p < 0.05 versus flow in sinus rhythm) and the vein graft flow (109.8 +/- 7.9 ml per min, p < 0.05 versus flow in sinus rhythm). The increases in flow in both cases were not attributable to changes in perfusion pressure. In contrast, ventricular pacing to the same heart rate decreased systemic pressure slightly, but insignificantly. Despite the slight decrease in perfusion pressure, ventricular pacing increased ITA flow (107.9 +/- 8.4 ml per min, p < 0.05 versus flow in sinus rhythm), but the increase in vein graft flow was not significant compared with flow in sinus rhythm (102.1 +/- 7.3 ml per min, p = ns versus flow in sinus rhythm).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Successful small diameter arterial grafting using cryopreserved allograft arteries.

Intimal hyperplasia (IH) limits the long-term success of veins as arterial grafts. IH occurs in veins partly as an adaptive process to arterial pressure conditions. The authors have previously reported early success with cryopreserved (CP) saphenous veins as aortocoronary bypass grafts, and they have hypothesized that CP arterial segments were already structurally adapted for arterial conditions. Six femoral arterial segments were harvested from three adult donor dogs, and cryopreserved. The segments were thawed and implanted into six recipient dogs, in end-to-end fashion, as interpositional grafts in the femoral artery. A similar length of native femoral artery was removed from the implant site and grafted in the contralateral femoral artery of the same animal to serve as native autograft-matched controls. Grafts were harvested bilaterally after 2 (n = 3) and 4 weeks (n = 3), perfusion fixed (80 mmHg, 15 min), and analyzed histologically. All grafts were patent at harvest, and flows distal to the grafted segments were not significantly different between grafts within an animal either at implant or subsequent harvest. Although CP arterial grafts still showed slight but significant dilation compared with native autograft, the dilation was much less than seen previously with either CP or native venous segments. No evidence of inflammation or IH was seen in CP arterial grafts. The absence of early IH or inflammation suggests that CP small diameter arteries may perform better than many currently available allograft tissues and synthetic prosthetics.

Animals↗