All amniotes except birds and mammals have the ability to shunt blood past the lungs, but the physiological function of this ability is poorly understood. We studied the role of the shunt in digestion in juvenile American alligators in the following ways. First, we characterized the shunt in fasting and postprandial animals and found that blood was shunted past the lungs during digestion. Second, we disabled the shunt by surgically sealing the left aortic orifice in one group of animals, and we performed a sham surgery in another. We then compared postprandial rates of gastric acid secretion at body temperatures of 19 degrees and 27 degrees C and rates of digestion of bone at 27 degrees C. Twelve hours after eating, maximal rates of gastric acid secretion when measured at 19 degrees and 27 degrees C were significantly less in the disabled group than in sham-operated animals. Twenty-four hours postprandial, a significant decrease was found at 27 degrees C but not at 19 degrees C. For the first half of digestion, dissolution of cortical bone was significantly slower in the disabled animals. These data suggest the right-to-left shunt serves to retain carbon dioxide in the body so that it can be used by the gastrointestinal system. We hypothesize that the foramen of Panizza functions to enrich with oxygen blood that is destined for the gastrointestinal system to power proton pumps and other energy-demanding processes of digestion and that the right-to-left shunt serves to provide carbon dioxide to gastrointestinal organs besides the stomach, such as the pancreas, spleen, upper small intestine, and liver.

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This article presents an integrated model of the human circulatory system that incorporates circulatory support by a brushless DC axial flow ventricular assist device (VAD), and a feedback VAD controller designed to maintain physiologically sufficient perfusion. The developed integrated model combines a network type model of the circulatory system with a nonlinear dynamic model of the brushless DC pump We show that maintaining a reference differential pressure between the left ventricle and aorta leads to adequate perfusion for different pathologic cases, ranging from normal heart to left heart asystole, and widely varying physical activity scenarios from rest to exercise.

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A ventricular assist device (VAD), which is a miniaturized axial flow pump from the point of view of mechanism, has been designed and studied in this report. It consists of an inducer, an impeller, and a diffuser. The main design objective of this VAD is to produce an axial pump with a streamlined, idealized, and nonobstructing blood flow path. The magnetic bearings are adapted so that the impeller is completely magnetically levitated. The VAD operates under transient conditions because of the spinning movement of the impeller and the pulsatile inlet flow rate. The design method, procedure, and iterations are presented. The VAD's performance under transient conditions is investigated by means of computational fluid dynamics (CFD). Two reference frames, rotational and stationary, are implemented in the CFD simulations. The inlet and outlet surfaces of the impeller, which are connected to the inducer and diffuser respectively, are allowed to rotate and slide during the calculation to simulate the realistic spinning motion of the impeller. The flow head curves are determined, and the variation of pressure distribution during a cardiac cycle (including systole and diastole) is given. The axial oscillation of impeller is also estimated for the magnetic bearing design. The transient CFD simulation, which requires more computer resources and calculation efforts than the steady simulation, provides a range rather than only a point for the VAD's performance. Because of pulsatile flow phenomena and virtual spinning movement of the impeller, the transient simulation, which is realistically correlated with the in vivo implant scenarios of a VAD, is essential to ensure an effective and reliable VAD design.

We synthesized a series of octapeptide analogs of somatostatin, containing N-terminal tryptophan or another amino acid followed by the hexapeptide sequences Cis-Phe-D-Trp-Lys-Thr-Cjs or Cis-Tyr-D-Trp-Lys-Val-Cys and a C-terminal threoninamide or tryptophanamide. After purification by HPLC, the inhibitory activities of these analogs on the release of growth hormone (somatotropin) in rats were determined in vivo. The eight octapeptides with an N-terminal tryptophan residue were found to have a greater inhibitory effect than somatostatin. hr. In view of their high activity and prolonged duration of action, some of these analogs could be useful clinically.Tetradecapeptide somatostatin is of little therapeutic value, because of its short half-life and broad spectrum of biological actions (1). Earlier structure-activity studies on somatostatin revealed that the entire molecule was not required for the maintenance of the biological activity of this peptide (2). Some somatostatin analogs containing modification of showed higher potency, but they exhibited a rapid inactivation in vivo (3,4). From a number of cyclic analogs synthesized by Veber et al. (5,6), the hexapeptide cyclo(-N-MeAla-Tyr-D-Trp-Lys-Val-Phe-) was found to be 50-100 times more potent than somatostatin in tests on the inhibition of growth hormone (GH, somatotropin), insulin, and glucagon release in vitro.Another potent somatostatin analog is the octapeptide D-Phe-Cys-Phe-D-Trp-Lys-Thr-Cys-Thr(ol) (7). This analog has not only a greater potency and duration of action on GH release but also a more selective effect on insulin and glucagon release. The suppressive action of this compound on GH release was found to be more selective than the inhibitory effect on insulin and glucagon secretion (7). Various analogs related to this octapeptide but containing tyrosine and valine at positions 3 and 6, respectively, and threoninamide or tryptophanamide at position 8 were synthesized in our laboratory (8, 9). These analogs showed a high potency and protracted duration of action on the inhibition of GH release in vivo. This paper reports the synthesis and the evaluations of biological activity of octapeptide somatostatin analogs containing various N-terminal substitutions.MATERIALS AND METHODS Synthesis. The analogs were synthesized in a Beckman model 990 automatic peptide synthesizer or in the usual glass reaction vessels, using standard solid-phase procedures (10). Benzhydrylamine resin (0.50 mmol/g, Bachem, Torrance, CA) was used as starting material. Amino acids (Bachem) were coupled as their Na-tert-butoxycarbonyl (Boc) derivatives. The reactive side chains were protected as follows: serine and threonine, with benzyl; cysteine, with 4-methylbenzyl; lysine, with 2-chlorobenzyloxycarbonyl; tyrosine, with 2-bromobenzyloxycarbonyl. Stepwise coupling using carbodimide was performed in methylene chloride or other solvents. After the incorporation of tryptophan, 2-mercaptoethanol was added to the 50% CF3COOH/50% CH2C12 (vol/vol) solution in all subsequent debl...

The number of research institutions using calves and sheep as models for open heart surgical procedures is increasing. The Artificial Heart Laboratory of the University of Utah has developed an effective protocol for thoracic procedures in these animals. Routine barbiturate induction and maintenance with fluothane and a pressure-regulated ventilator have minimized anesthetic problems. A membrane oxygenator with blood flows of 50 to 75 ml/kg body weight/min. seems to give adequate circulatory support during heart-lung bypass. Although animals implanted with total artificial hearts do not have problems with arrhythmias, changes in pulmonary function and peripheral vascular tone can alter their cardiac performance. The judicious use of ventilatory support and specific vasoactive drugs can significantly improve the animal's intraoperative blood pressure and postoperative arterial gases. A summary of the techniques and drugs which were used successfully in 187 of 189 animals during a 2 year period are presented.

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