PubMed Health⌕ Search

Biomedical subjects

S Popilskis

Publications and source records attributed to S Popilskis.

8 recordsLinked to original sources

The role of angiotensin II AT1 receptor in the maintenance of hemodynamics in a canine model of coronary microembolization-induced heart failure.

The purpose of this study was to determine whether Angiotensin II (Ang II) contributes to the regulation of resting hemodynamics via Ang II type 1 (AT1) receptors in awake dogs with coronary microembolization-induced heart failure. Six dogs were surgically instrumented for measurement of systemic hemodynamics and for coronary microembolization. The acute hemodynamic effects of a selective AT1-receptor antagonist, GR138950 (1 mg/kg, i.v.), were determined before and after congestive heart failure (CHF). GR138950 had no effects on hemodynamics before CHF Daily coronary microembolizations (through the previously implanted coronary catheter) resulted in CHF, as documented by hemodynamic measurements, a slight but significant increased Ang II plasma level (17.4 +/- 1.6 vs. 23 +/- 1.0 pg/ml; p < 0.05), and characteristic clinical signs of CHF. After CHF, GR138950 significantly increased left ventricular dP/dt(max) (LVdP/dt(max)) from 1,754 +/- 68 to 2,347 +/- 114 mm Hg/s and decreased LV systolic pressure (LVSP) from 118 +/- 5 to 101 +/- 7 mm Hg; meanwhile, heart rate (from 132 +/- 4 to 102 +/- 6 beats/min) and LV end-diastolic pressure (LVEDP; from 17 +/- 3 to 9 +/- 1.5 mm Hg) were significantly decreased. Mean arterial pressure (MAP) was not affected. The peak effects occurred 90 min after administration. Thus Ang II contributes significantly to resting hemodynamics via AT1 receptors in this CHF model; that is, the specific AT1 blocker inhibits the negative inotropic actions of Ang II in the CHF state.

Angiotensin II↗

Coronary endothelial dysfunction precedes heart failure and reduction of coronary reserve in awake dogs.

Endothelial dysfunction in coronary circulation is well documented in heart failure (HF). However, whether this dysfunction is a consequence of heart failure or precedes the development of HF remains unknown. To determine endothelium-dependent regulation in the remote coronary vasculature in a canine coronary microembolization-induced HF model, seven dogs were chronically instrumented for measurement of systemic hemodynamics, for selective coronary microembolization via an implanted coronary catheter and for measurement of coronary blood flow in the non-embolized coronary artery. Microembolizations were performed daily until hemodynamic and echocardiographic measurements showed HF. The responses of coronary blood flow to acetylcholine (0.25, 0.5, 5, 10 microg/kg), nitroglycerin (0.2, 0.8, 5, 25 microg/kg), adenosine (0.25, 0.5, 2, 5 micromol/kg) and brief coronary occlusions (5, 10, 15, 20, 30 s) were examined. Although no signs of HF developed and the responses of coronary blood flow to nitroglycerin, adenosine and occlusions were not altered, the response to acetylcholine was selectively reduced after 1 week of embolization (275,000+/-55,000 microspheres). Resting coronary flow increased from 21.3+/-1.4 ml/min in control state to 27.7+3.5 ml/min (P<0.001). As HF developed, characterized by an elevated left ventricular end-diastolic pressure (6.4+/-1.6 v 16+/-1.6 mmHg, P<0.001), a decreased area ejection fraction (54+/-5 v 36+/-5%, P<0.05) and a reduced beta-adrenergic response to isoproterenol, the responses of coronary blood flow to acetylcholine, nitroglycerine, adenosine and occlusions were consistently depressed. Resting coronary blood flow was decreased to 15.4+/-2.7 ml/min (P<0.01). Our results indicate, that there is a selectively impaired endothelium-mediated dilator capacity of the resistance coronary vasculature before the development of HF and a reduction of the coronary flow reserve.

Acetylcholine↗

Modified technique for heterotopic heart transplantation in small primates.

Cardiac transplantation in small primates represents a unique model for investigating both xenograft and allograft rejection. This report describes our technique for heterotopic transplantation of cardiac grafts into the retroperitoneal iliac vessels of newborn baboons and small primates. Small primates tolerate this position better than either cervical or abdominal placement.

Animals↗

FOS expression in the gonadotropin-releasing hormone (GnRH) neuron does not increase during the ovarian steroid-induced GnRH surge in the rhesus monkey.

The purpose of this study was to investigate the expression of the immediate early gene, c-fos, in GnRH neurons in female rhesus monkeys as a function of generation of the LH surge. Adult monkeys were either intact (n = 6) or ovariectomized (n = 10). Intact animals received estradiol benzoate (EB; 330 micrograms in oil, sc; n = 5) or oil (n = 1). Ovariectomized animals received either EB (n = 5) or EB, followed by progesterone (P; 2.5 ml in oil, im; n = 4), or oil (n = 1). Animals were killed from 31-75 h after EB treatment. Blood samples were collected to document LH release in response to steroid treatment. A surge of LH was initiated in most animals that received EB alone or EB plus P about 30 h after steroid treatment. Animals were perfused with 4% paraformaldehyde, and brain blocks encompassing the region known to contain the majority of GnRH neurons (septum through the medial basal hypothalamus) were cut on the vibratome. Sites of FOS and GnRH immunoreactivities were demonstrated using double labels with a variety of chromogens. Regardless of the time in the surge, there were very few GnRH neurons with FOS immunoreactivity in their nuclei (0-9%). FOS-positive nuclei were seen in many other neurons in various brain regions, including the suprachiasmatic and supraoptic nuclei. There were no differences in FOS expression in GnRH neurons in intact and ovariectomized animals or in steroid- or oil-treated animals. These results suggest that FOS activation in GnRH neurons is not associated with the initiation of the secretory GnRH stimulus to the LH surge in the rhesus monkey. If confirmed, these data suggest that the GnRH nerve terminal may be the primary site for the control of the GnRH surge.

Animals↗

Unilateral MPTP-induced parkinsonism in monkeys. A quantitative autoradiographic study of dopamine D1 and D2 receptors and re-uptake sites.

The cynomolgus monkeys received a unilateral intracarotid injection of the neurotoxin N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in order to induce a chronic model of hemi-parkinsonism. The procedure was well tolerated by the animals. Unilateral injection of MPTP caused rigidity and bradykinesia of the contralateral limbs, but the animals were able to eat and drink without levodopa therapy. During spontaneous motor activity, animals rotated toward the lesioned side whereas systemic apomorphine injection stimulated circling toward the normal non-lesioned side. Twelve weeks after MPTP injection, we found a marked reduction in striatal and nigral [3H]-mazindol binding on the MPTP-injected side which is indicative of a loss in both dopaminergic nerve terminals and cell bodies. The unilateral dopaminergic denervation was associated with an ipsilateral increase in striatal and a reduction in nigral [3H]-spiperone-labelled D2 dopamine receptors; these changes are consistent with the known localization of the D2 receptors on striatal dopaminergic nerve terminals and on nigral dopaminergic cell bodies. In contrast, no changes in [3H]-SCH 23390-labelled D1 dopamine receptors were observed at the level of either the striatum or the substantia nigra. This study describes a well tolerated procedure which induces a clinical and morphological hemi-parkinsonian syndrome. This animal model may be useful in the studies of new antiparkinsonian drugs, for testing the functional efficacy of brain tissue implants and in the understanding of the physiopathogenesis of levodopa-induced dyskinesias.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

In vivo comparison of THC:YAG laser welding to sutured closure of biliary tissue.

Percutaneous endoscopic approaches to cholelithiasis are an alternative to extracorporeal shockwave lithotripsy which offer advantages of fewer restrictions on stone size and type as well as avoidance of fragmented stone passage complications. Endoscopic techniques would be facilitated by methods of welding gallbladder tissues. The technical constraints imposed by the endoscopic approach favor nonsuture methods of fusing gallbladder tissues. To evaluate a laser method for fusing biliary tissue, we have compared the healing response of laser-welded versus polyglycolic acid suture-closed incisions in canine gallbladder tissue in vivo. The laser used was a thulium-holmium-chromium:YAG laser producing 200-microsecond, 300-millijoule pulses at 2.15 microns. Serial sacrifice of dogs that underwent laser or suture closure of incisions made in the fundus of the gallbladder revealed that all repairs healed without evidence of leakage or infection. Laser-welded cholecystotomy sites had complete fibrous healing of the wound by two weeks postoperatively and reepithelialization by three weeks after operation. Suture-closed wounds were still without complete epithelization four weeks after the procedure. Laser welding may be a useful technique in endoscopic biliary surgery.

Animals↗

Epidural vs. intramuscular oxymorphone analgesia after thoracotomy in dogs.

Oxymorphone was administered epidurally (0.1 mg/kg) or intramuscularly (IM) (0.2 mg/kg) to 16 dogs undergoing thoracotomy, to compare the analgesic effectiveness. Heart rate, respiratory rate, systolic and diastolic blood pressure, and pain score were measured hourly. Arterial blood gases were measured at hour 1. A single dose of oxymorphone injected epidurally provided analgesia for up to 10 hours, whereas the IM route provided a comparable effect for less than 2 hours. There were statistically significant increases in heart rate, and systolic and diastolic blood pressures at hour 2 in the dogs treated IM over the dogs treated epidurally. We conclude that epidurally administered oxymorphone is highly effective in alleviating pain after thoracotomy in dogs and provides longer lasting analgesia than the IM route.

Analgesia, Epidural↗

Is preoperative fasting necessary?

The effects of fasting and of histamine (H2) antagonists on gastric volume and acidity were studied in 56 baboons undergoing various surgical procedures under general anesthesia and randomly allocated into 4 groups; group A--fasted for 14 hours; group B--given 100-120 ml of water 3 hours before surgery; groups C and D--also given 100-120 ml of water 3 hours before surgery; in addition, the former received cimetidine 10 mg/kg IM and the latter ranitidine 1.5 mg/kg IM 30-40 minutes before anesthesia. There were no significant differences between groups A and B with respect to the gastric volume and pH. Both ranitidine and cimetidine significantly (P < 0.02) reduced gastric volume and increased gastric pH. Thus, prolonged withholding of oral fluids does not reduce the gastric volume or increase gastric pH. H2-antagonists are effective in reducing both gastric residual volume and pH.

Animals↗