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Biomedical subjects

M Carrier

Publications and source records attributed to M Carrier.

At least 109 records · Page 6Linked to original sources
PubMed1997

Pharmacokinetic, hemodynamic, and metabolic effects of cyclosporine sandimmune versus the microemulsion neoral in heart transplant recipients.

BACKGROUND: Cyclosporine is a potent immunosuppressive agent that is, however, associated with systemic hypertension and renal dysfunction. The purpose of this investigation was to study the pharmacokinetic and long-term renal and hypertensive effects of Sandimmune (Sandoz) versus the new Neoral (Novartis) formulation of cyclosporine in heart transplant recipients. METHODS: Twenty heart transplant recipients with stable conditions and aged 54 +/- 9 years were studied in an open-labeled single-arm conversion protocol. Twelve-hour pharmacokinetic studies were performed on Sandimmune and after 4 weeks of treatment with Neoral at similar dosage. The 24-hour blood pressure monitoring, creatinine clearance, and complete biochemistry profile were studied simultaneously to the pharmacokinetic studies. Six-month follow-up with serial measurements of cyclosporine levels, and biochemistry profile was completed. RESULTS: Conversion to Neoral resulted in a 24% increase in area-under-the-curve in spite of no significant changes in cyclosporine trough levels (165 +/- 48 [Sandimmune] vs 169 +/- 32 nmol/L; p = 0.26). Respectively, 16%, 68%, and 16% were poor, average, and good absorbers on Sandimmune versus 26% and 74% being average or good absorbers on Neoral. Averaged systolic and diastolic blood pressure were not affected by Neoral, but blood pressure readings increased in 20% of patients previously known as having hypertension. The 24-hour blood pressure data yielded no significant changes with Neoral, but the nocturnal drop in systolic blood pressure was attenuated by Neoral. Twenty-four-hour creatinine clearance was not affected by Neoral, but serum magnesium levels decreased significantly at 6 months. CONCLUSIONS: Neoral resulted in 24% increase in cyclosporine exposure without significant changes in trough levels, and improved absorption status. This greater drug exposure is well tolerated and resulted in a slight increase in blood pressure in a subset of patients and some decrease in magnesium levels, but it had no effect on renal function.

Adult↗
PubMed1997

[Clinical results of peroperative transesophageal echography in peri-valvular leaks of heart prosthesis].

Perivalvular leaks following prosthetic valve replacement are associated with significant morbidity. Management has classically consisted of valve replacement or blind surgical repair. Our study examines the results of intraoperative transesophageal echo-guided repair of perivalvular leaks (ITEGR). Between November 24, 1987 and January 1st, 1996, 23 patients (10 men, 13 women) at the Montreal Heart Institute underwent ITEGR. Ninety percent were NYHA class III-IV preoperatively. Seventy to 85% had significant cardiac insufficiency preoperatively. Eighty-six percent of the leaks were in the mitral valve location, 90% of which were mechanic prosthesis. Eighty-nine percent of patients had hemolysis with an average LDH of 720. Mean bypass time was 125 minutes with a mean clamp time of 77 minutes. Most patients were undergoing a third operation at the time of repair. Operative mortality was 8%, all due to biventricular failure. A mean follow-up of 67 months showed a late death of 10%. Of the 19 survivors, 77% were NYHA class I-II. Overall mortality was 20%. In our institution valve re-replacement in similar circumstances was associated with an operative and long-term mortality of 7% and 26% respectively. We conclude that intraoperative transesophageal echo-guided repair is an excellent management alternative in patients with perivalvular leaks with decreased late and overall mortality.

Adult↗
PubMed1996

Cyclosporin A-induced coronary artery vasoconstriction through myogenic and endothelium-dependent mechanisms.

BACKGROUND: The exact mechanism of vascular toxicity of cyclosporin A (CSA) remains unknown. It has been reported that an impairment of endothelium-mediated vascular reactivity may be involved. METHOD AND RESULTS: We studied the response to intracoronary injections of acetylcholine (ACh) (30 ng/kg), adenosine (100 ng/kg), and nitroglycerin (NTG) (1.7 micrograms/kg) before and after intracoronary infusion of CSA (20 mg over 20 minutes) and of L-arginine (10 mg.kg-1.min-1). Experiments were performed on 11 open-chest dogs anesthetized and instrumented for measurements of coronary blood flow (CBF) in the left anterior descending (LAD) and left circumflex (LCx) coronary arteries, left ventricular dP/dt, mean aortic pressure, and coronary sinus pressure. CSA, L-arginine, ACh, adenosine, and NTG were injected into the LAD, and the LCx served as control. The increase in CBF in the LAD with ACh administration averaged 21 +/- 11 mL/min before CSA, 15 +/- 10 mL/min after CSA, and 15 +/- 8 mL/min during L-arginine injection (P = .2). Adenosine caused an increase in CBF in the LAD averaging 20 +/- 10 mL/min before CSA, 10 +/- 8 mL/min after CSA, and 17 +/- 12 mL/min during L-arginine injection (P = .004). NTG caused an increase in CBF in the LAD averaging 21 +/- 10 mL/min before CSA, 13 +/- 11 mL/min after CSA, and 14 +/- 7 after administration of L-arginine (P = .009). CONCLUSIONS: These results suggest that direct intracoronary injection of CSA induces a vasoconstrictive response through endothelium-dependent and myogenic mechanisms. The muscarinic endothelial response was not affected by CSA, whereas the purinergic action of CSA was restored after L-arginine administration.

Acetylcholine↗
PubMed1996

Clinical trial of retrograde warm blood reperfusion versus standard cold topical irrigation of transplanted hearts.

BACKGROUND: A prospective, randomized clinical study involving 34 patients undergoing heart transplantation compared myocardial preservation of donor hearts maintained with continuous reperfusion with retrograde warm blood cardioplegia during surgical implantation versus the standard cold topical irrigation. METHODS: Hearts in both groups were arrested with a standard crystalloid solution and maintained in a cold saline solution during transportation. In the retrograde group, cardioplegia was administered through a catheter in the coronary sinus during surgical implantation. An average of 471 +/- 30 mL of hyperkalemic crystalloid solution diluted 1:4 in warm blood from the oxygenator was infused. In the standard group, the heart was kept cold by topical irrigation of cold saline solution and was reperfused only when the ascending aorta was unclamped. RESULTS: Preoperative characteristics of donors and recipients were similar in the two cohorts. Ischemic time average 139 +/- 12 minutes in the retrograde group compared with 130 +/- 11 minutes in the standard group (p = 0.57). Cardiopulmonary bypass time averaged 89 +/- 4 minutes in the retrograde group and 110 +/- 12 minutes in the standard group (p = 0.12). Defibrillation at reperfusion was performed in 4 patients (4/17, 24%) in the retrograde group and 12 patients (12/18, 67%) in the standard group (p = 0.01). There were no deaths in the retrograde group (0/17), whereas in the standard group, 3 patients (3/17) died of early graft failure (p = 0.11). Four early graft failures occurred in the standard group (p = 0.06). Two patients (2/17, 12%) were weaned from bypass with ventricular assist devices in the standard group. The number of subendocardial necrotic cells in the first two weekly endomyocardial biopsy specimens averaged 2.7 +/- 0.8 cells/mm2 in the retrograde group and 5.9 +/- 2.4 cells/mm2 in the standard group (p = 0.12). CONCLUSIONS: Retrograde warm blood reperfusion appears to improve the initial recovery of transplanted hearts. The technique is easy to use and may be a useful approach to graft protection during surgical implantation.

Adult↗
PubMed1996

Effect of L-arginine on metabolic recovery of the ischemic myocardium.

BACKGROUND: The release of nitric oxide is decreased after myocardial ischemia and reperfusion. Whereas the precursor L-arginine can stimulate the release of nitric oxide, its effect on metabolic recovery after myocardial ischemia is unknown. METHODS: To study the effect of L-arginine on metabolic recovery after myocardial ischemia, cardioplegia infusion, and reperfusion, 33 dogs were placed on cardiopulmonary bypass and subjected to a sequence of 30 minutes of normothermic global ischemia, 30 minutes of warm blood cardioplegic arrest, and 30 minutes of reperfusion. A pH probe was inserted in the anterior wall of the left ventricle, and tissue pH was measured throughout the experiment. Coronary blood flow in the left anterior descending coronary artery and the circumflex coronary artery was measured. Blood samples from the coronary sinus were taken to measure blood pH and levels of lactate, creatine kinase, and troponin T. RESULTS: In the control group of 9 dogs, tissue pH averaged 6.4 +/- 0.1, 6.5 +/- 0.1, and 6.8 +/- 0.1 after the end of global ischemia, cardioplegia, and reperfusion, respectively. Tissue pH averaged 6.4 +/- 0.1, 6.6 +/- 0.1, and 6.9 +/- 0.1, respectively, in the experimental group of 9 animals with 2 mmol/L of L-arginine added to the cardioplegic solution. Tissue pH averaged 6.2 +/- 0.1, 6.7 +/- 0.1, 7.1 +/- 0.1, respectively, in the third group of 9 animals that received an additional infusion of L-arginine (10 mg.kg-1.min-1) during reperfusion. Tissue pH recovered faster in groups with L-arginine (p = 0.00001). A hyperemic response of coronary blood flow was shown at reperfusion in animals in the control group only. In 6 dogs, L-NAME (N-nitroarginine methyl ester), an inhibitor of nitric oxide synthesis, was injected and resulted in a slower pH recovery on reperfusion compared with that of animals that received L-arginine. CONCLUSIONS: The addition of L-arginine to the cardioplegic solution and the systemic circulation during reperfusion resulted in a significant increase in coronary blood flow during cardioplegia infusion and in a faster recovery of myocardial tissue pH, possibly by increasing coronary blood flow through the release of nitric oxide.

Animals↗
PubMed1996

Evidence for two components of delayed rectifier K+ current in human ventricular myocytes.

Previous voltage-clamp studies have suggested that the delayed rectifier current (IK) is small or absent in the human ventricle and, when present, consists only of the rapid component (IKr); however, molecular studies suggest the presence of functionally important IK in the human heart, specific IKr blockers are known to delay ventricular repolarization and cause the long QT syndrome in humans, and we have shown that the expression of IK is strongly influenced by cell isolation techniques. The present experiments were designed to assess the expression of IK in myocytes obtained by arterial perfusion of right ventricular tissue from explanted human hearts. Of 35 cells from three hearts, 33 (94%) showed time-dependent currents typical of IK. The envelope-of-tails test was not satisfied under control conditions but became satisfied in the presence of the benzenesulfonamide E-4031 (5 micromol/L). E-4031 suppressed a portion of IK in 32 of 33 cells, with properties of the drug-sensitive and -resistant components consistent with previous descriptions of IKr and the slow component (IKs), respectively. Action potential duration to 95% repolarization at 1 Hz was prolonged by E-4031 from 336+/-16 (mean +/- SEM) to 421 +/- 19ms (n = 5, P < .01), indicating a functional role for IK. Indapamide, a diuretic agent previously shown to inhibit IKs selectively, suppressed E-4031-resistant current. The presence of a third type of delayed rectifier, the ultrarapid delayed rectifier current (IKur), was evaluated with the use of depolarizing prepulses and low concentrations (50 micromol/L) of 4-aminopyridine. Although these techniques revealed clear IKur in five of five human atrial cells, no corresponding component was observed in any of five human ventricular myocytes. We conclude that a functionally significant IK, with components corresponding to IKr and IKs, is present in human ventricular cells, whereas IKur appears to be absent. These findings are important for understanding the molecular, physiological, and pharmacological determinants of human ventricular repolarization and arrhythmias.

4-Aminopyridine↗
PubMed1996

Coronary Angioplasty in the Treatment of Post-Cardiac Transplant Coronary Artery Disease.

Accelerated coronary disease following cardiac transplantation is an important obstacle to long-term survival and its management is not well defined. Coronary angioplasty has been proposed as a palliative treatment in some patients with discrete proximal lesions. Of 172 patients who underwent cardiac transplantation between April 1983 and November 1995, 8 underwent subsequent coronary angioplasty of 11 lesions. The majority was performed in asymptomatic patients, 5 for angiographic abnormalities alone, and 3 for documented painless ischemia. Primary angiographic success was obtained in 91% (10/11) of lesions dilated. Complications included 1 acute occlusion and 1 arteriovenous fistula. Three patients died, 1, 8 and 10 months after angioplasty. After an average of 36-month follow-up, 4 (out of 8) patients had no cardiac event (myocardial infarction, second angioplasty, retransplantation or death). Thus, coronary angioplasty can be performed with acceptable risk in selected patients with cardiac transplantation.

Journal Article↗
PubMed1996

Metabolic recovery after global myocardial ischemia: effects of blood cardioplegic solutions.

OBJECTIVE: To determine the effect of whole blood cardioplegia (WBC) and a mix of crystalloid in blood (CB) hyperkalemic cardioplegic solutions on recovery of the myocardium following global ischemia. DESIGN: Twenty-one dogs were placed on normothermic cardiopulmonary bypass, and a pH probe was inserted in the anterior wall of the left ventricle. Global myocardial ischemia was obtained by clamping the ascending aorta until a decrease in myocardial tissue pH of 0.4 units from baseline value was obtained, at which time cardioplegic solutions were perfused over 30 mins. The aorta was then unclamped and 30 mins of reperfusion was allowed. RESULTS: The aortic cross-clamping time necessary to decrease myocardial tissue pH 0.4 units from baseline averaged 13 +/- 8 mins. Whereas myocardial tissue pH returned to baseline value (6.9 +/- 0.1) after an average of 24 mins with cold (15 degrees C) and warm (35 degrees C) WBC, it took an average of 48 mins to reach control levels when warm CB solutions were used. Moreover, tissue pH decreased temporarily from 6.97 +/- 0.35 to 6.77 +/- 0.37 (P < 0.05) at initiation of normothermic myocardial reperfusion in cold WBC protected animals, and myocardial pH remained normal in the warm WBC group but remained severely acidic in warm CB animals (6.6 +/- 0.3). CONCLUSIONS: Metabolic recovery after global ischemia was faster with WBC cardioplegic protection. Normothermic blood reperfusion in cold WBC protected animals caused a significant but temporary tissue acidosis.

Animals↗
PubMed1996

Receptor-specific effects of acute rejection after heart transplantation on endothelium-dependent coronary relaxation in dogs.

To establish the effects of acute rejection on coronary artery endothelial reactivity in a canine model of heart transplantation, we submitted seven mongrel dogs to heterotopic heart transplantation without immunosuppression for a period of 7 days. At harvesting, all transplanted hearts displayed a grade IV histologic rejection. Compared with native heart, the endothelium-dependent relaxation of the coronary arteries from the graft displayed an increased sensitivity to serotonin, a decreased sensitivity to thrombin, and no change in the response to acetylcholine and adenosine diphosphate; endothelium-independent relaxation to sodium nitroprusside was not affected. Therefore, in the canine heterotopic heart transplant model, acute rejection has no effect on endothelium-independent relaxation of coronary arteries but affects endothelium-dependent relaxation in a receptor-specific manner.

Acetylcholine↗
PubMed1996

Effect of pentoxifylline on renal toxicity of cyclosporine: results of a clinical trial after heart transplantation.

BACKGROUND: Pentoxifylline was suggested to prevent the renal release of endothelin caused by cyclosporine. METHODS: We studied the renal-sparing effect of pentoxifylline in 44 patients who underwent heart transplantation between 1991 and 1994 and were randomized to a group treated with pentoxifylline (400 mg three times daily) or to a control group. All patients were treated according to the same immunosuppression protocol, including induction with perioperative rabbit anti-thymocyte antibody and maintenance with azathioprine, cyclosporine, and prednisone. Five patients withdrew voluntarily because of lack of compliance, and five patients died during the first month of the study. RESULTS: There was no difference between the two groups in regard to age, sex, initial cardiopathy, the number of acute rejections, and the number of infection episodes. Urinary clearance of creatinine averaged 1.1 +/- 0.1 ml/sec, 1.3 +/- 0.1 ml/sec, and 1.3 +/- 0.1 ml/sec in the control patients (n = 16) and 1.2 +/- 0.1 ml/sec, 1.4 +/- 0.1 ml/sec, and 1.3 ml/sec in patients treated with pentoxifylline (n = 18) at initiation, 12 months, and 24 months of the study (p > 0.05), respectively. At these three times, the serum creatinine levels averaged 106 +/- 4 mmol/L, 119 +/- 4 mmol/L, and 126 +/- 5 mmol/L in the control group and 94 +/- 4 mmol/L, 114 +/- 4 mmol/L, and 127 +/- 5 mmol/L in patients treated with pentoxifylline, respectively (p > 0.05). Trough levels of cyclosporine throughout the study period averaged 212 +/- 8 mmol/L and 206 +/- 8 mmol/L in the control and treated groups, respectively (p > 0.05). Endothelin blood levels averaged 0.4 +/- 0.2 pg/ml for nine control patients and 0.4 +/- 0.1 pg/ml for a group of 10 patients treated with pentoxifylline (p > 0.05). CONCLUSIONS: Pentoxifylline in association with cyclosporine did not result in a significant improvement in renal function during the first 2 years after heart transplantation.

Creatinine↗
PubMed1996

[Effect of cyclosporin A on the reactivity of the pulmonary vascular network in dogs].

UNLABELLED: Aside to its immunosuppressive effects, cyclosporine A (CyA) is known as a vasoconstrictor agent. The vasoconstriction appears to be related to an endothelial release of thromboxane A2 (TxA2) and endothelium as well as a decrease endothelial production of nitric oxide. However, no data is available on the effects of CyA on pulmonary artery (PA) network. We designed experiments to study the CyA effects on canine pulmonary artery vasoregulation. Resistance vessels were studied in vivo using a lung (n = 6) steady rate delivery autoperfusion model. The CyA was infused in the left pulmonary artery at incremental doses of 5, 10, and 20 mg; CyA dosage, sampled in the left atrium, were respectively 515 +/- 67, 580 +/- 97, and 1024 +/- 84 nmol/L. No significant increase in tension were registered regardless of the dose infused. Conductance vessels were studied in vitro using third division PA segments (n = 6) suspended for isometric force measurement in organ chambers. PA segments were precontracted (phenylephrine 10(-6) M) and subsequently exposed to incremental dose of CyA and cremophor (CR), the CyA vehicle. CyA specifically induced a dose-dependent contraction. The maximal contraction observed were 159 g +/- 13% with CyA exposure and 106 +/- 3% with the CR (p < 0.05). This contraction was abolished by indomethacin (cyclooxygenase inhibitor), pinane thromboxane A2 (TxA2 antagonist), dexamethasone (phospholipase A2 inhibitor), neomycin (phospholipase C inhibitor), and endothelial mechanical denudation. CONCLUSIONS: In the canine model, in vivo infusion of CyA does not affect pulmonary resistance arteries. However, in vitro, on pulmonary conductance arteries, CyA induces an endothelium-dependent vasoconstriction. This constriction appears to be related to a TxA2 release mediated by a phospholipase A2 phospholipase C pathway.

Animals↗
PubMed1995

The Carpentier-Edwards pericardial bioprosthesis: clinical experience with 600 patients.

Carpentier-Edwards pericardial bioprostheses were implanted in 600 patients: 416 aortic valve replacement, 115 mitral valve replacement, 6 isolated tricuspid, and 63 multiple valve replacements. The survival rates were 70% at 10 years after aortic valve replacement, 62% 8 years after mitral valve replacement, and 57% at 8 years with multiple valve replacement. Overall, 69 patients suffered one or more valve-related complications. The 10-year freedom rates from embolism were 91% (aortic valve replacement), 92% (mitral valve replacement), and 89% (multiple valve replacement), and those from endocarditis were 95%, 93%, and 85%, respectively. In 18 of the 35 patients, reoperation was due to primary valve dysfunction. Freedom from primary dysfunction was 87% at 10 years with aortic valve replacement, and at 8 years, it was 79% with mitral valve replacement and 77% with multiple valve replacement. A direct correlation was found between freedom from valve dysfunction and age of the patient at operation, with a 10-year-free rate of 90% among patients older than 59 years. This bioprosthesis has an excellent durability up to 10 years in the aortic position. More data regarding its long-term durability in the mitral position are needed. It is currently our valve substitute of choice when a bioprosthesis is indicated.

Actuarial Analysis↗
PubMed1995

Antithymocyte globulin and methotrexate therapy of severe or persistent cardiac allograft rejection.

BACKGROUND: The treatment of severe or persistent acute rejection remains difficult despite newer immunosuppressive agents available. METHODS: To evaluate the effectiveness of rabbit antithymocyte globulin and methotrexate as therapy for severe or persistent acute cardiac allograft rejection, we conducted a retrospective analysis of clinical and laboratory data from 150 consecutive heart transplant recipients between 1983 and 1994. RESULTS: Thirteen episodes of severe or refractory acute rejection were treated with rabbit antithymocyte globulin in 10 patients. Rabbit antithymocyte globulin (125 mg/day for 3 consecutive days) was effective in 90% of patients. Therapy was well tolerated, and contributed to one infectious complication, no malignancy, and long-term survival in 8 of 10 patients. Recurrent rejection developed in 60% of patients. Methotrexate (7.5 to 15 mg/wk for 16 weeks) was administered to 8 patients with persistent rejection documented on three consecutive endomyocardial biopsies. Therapy was effective in 6 of the 8 patients, with one infectious complication and no malignancy on follow-up. White blood cell count decreased significantly during therapy (p = 0.008). Seven of the 8 patients in the methotrexate group are long-term survivors. CONCLUSIONS: Rabbit antithymocyte globulin is a valuable alternative in patients with severe or refractory acute rejection. Methotrexate is an important adjunct in patients with persistent rejection unresponsive to conventional immunosuppressive regimens.

Adult↗
PubMed1995

2,3-Butanedione monoxime preserves coronary artery endothelium-dependent relaxation during myocardial ischemia in the isolated rat heart.

OBJECTIVE: To evaluate the potential benefit of 2,3-butanedione monoxime (BDM) in preserving endothelium-dependent coronary artery relaxation during myocardial ischemia. MATERIALS AND METHODS: Langendorff-perfused rat heart model. Endothelium-dependent and independent relaxations were tested with infusion of 5-hydroxytryptamine (10(-6) mol/L) and sodium nitroprusside (10(-5) mol/L), respectively. Four groups of hearts (n = 6) were used. Group 1 was perfused with BDM (25 mmol/L) without ischemia for 30 mins. Group 2 was perfused for 10 mins with BDM and exposed to 30 mins of no flow ischemia (37 degrees C). Group 3 was perfused with cold (4 degrees C) nonoxygenated BDM (30 mins) and group 4 (control) was exposed to 30 mins of no flow ischemia alone. Left ventricular pressure (LVP), left ventricular pressure first derivative (dP/dt) and coronary basal flow were evaluated before treatment and after 30 mins of reperfusion. RESULTS: BDM perfusion alone (group 1) did not affect coronary reactivity. Preservation of endothelium-dependent and -independent relaxation was significantly enhanced after ischemia in groups 2 and 3 (BDM-treated) compared with group 4 (control). No significant benefit was found regarding LVP and dP/dt in all groups. Postreperfusion coronary flow was decreased in all hearts except the controls (group 4), suggesting a residual BDM intrinsic effect on coronary flow. CONCLUSION: These experiments suggest that BDM can enhance preservation of coronary artery endothelium-dependent and -independent relaxation during myocardial ischemia in the isolated rat heart.

Animals↗
PubMed1995

[Cyclosporine A decreases coronary blood flow in dogs].

The objective of the present study was to determine the effect of cyclosporine (CSA) on coronary artery reactivity. Six mongrel dogs, weighing 20 to 30 kg were anesthetized with sodium pentobarbital and were artificially ventilated. A median sternotomy was performed to expose the heart. Left anterior and circumflex coronary flows were measured with an electromagnetic flowmeter. Heart rate, mean arterial pressure, coronary sinus pressure and dP/dt were monitored during all experiments. Blood samples were withdrawn from the coronary sinus to measure CSA. Injections of 5 and 10 mg of CSA in the left anterior descending coronary artery were administered to all animals and the measure of the circumflex coronary blood flow was used as control during the experiments. The decrease in left anterior descending coronary artery blood flow averaged 24 +/- 9% (p = 0.002) and 18 +/- 11% (p = 0.009), and the increase in coronary vascular resistance averaged 31 +/- 12% (p = 0.005) and 16 +/- 24% (p = 0.1) after 5 and 10 mg of CSA, respectively. There were no significant changes in circumflex coronary artery blood flow and in dP/dt during the experiments. Cyclosporine blood levels averaged 453 +/- 226 nmol/l and 1087 +/- 199 nmol/l after injections of 5 and 10 mg of CSA, respectively. In conclusion, this study suggests that CSA can cause acute vasoconstriction of the arterial coronary vasculature.

Animals↗
PubMed1995

[Effect of the injection of cyclosporine A on the peripheral venous resistance in dogs].

We have studied the effect of cyclosporin on the peripheral venous system. CSA was injected into an isolated hind limb saphenous vein perfused at constant flow in 29 dogs. Reactivity of the vein was tested with infusions of norepinephrine (NE) before and after CSA. In a 1st group of 7 dogs, CSA at doses of 5, 10 and 20 mg was infused over a 10-minute period. In a 2nd group of 8 dogs, 20 mg of CSA was infused over 20 minutes and, injections of 6, 12 and 24 micrograms of NE were administered before and during CSA. In a 3rd (n = 7) and 4th (n = 7) groups of animals, 30 mg of CSA was injected over 60 minutes and injections of 3, 6, 12 micrograms of NE were given before and during CSA. In the last group, an ipsilateral lumbar sympathectomy was performed before CSA injection. The infusion of CSA over periods of 10 and 20 minutes did not cause significant changes in venous perfusion pressure. The infusion of 30 mg of CSA over 60 minutes caused an increase in venous perfusion pressure from 44 +/- 2 mm Hg to 58 +/- 5 mm Hg (p < 0.0001). Surgical sympathectomy prevented the venoconstrictor response to CSA. Injections of 3, 6 and 12 +/- g of NE caused averaged increases of 25 +/- 6, 39 +/- 9 and 53 +/- 10 mm Hg before CSA, and of 45 +/- 7, 69 +/- 12 and 84 +/- 8 mm Hg respectively after CSA injections, a significant increase (p = 0.03). In conclusion, CSA causes a vasoconstriction of the saphenous vein through stimulation of the sympathetic nervous system and potentiates the venoconstrictor effect of NE.

Animals↗