Terlipressin, a provasopressin drug exhibits direct vasoconstrictor properties: consequences on heart perfusion and performance.

OBJECTIVE: Terlipressin has been proposed as an alternative treatment to catecholamines to restore blood pressure in septic shock. Terlipressin is considered as a vasopressin prodrug capable of releasing small but sustained amounts of [Lysine] vasopressin (LVP) and to provide prolonged biological effect. However, terlipressin may act as a direct vasopressor beyond its conversion into LVP. We investigated terlipressin direct vasoconstrictive properties and consequences on myocardial perfusion and performance. DESIGN: Experimental studies. SETTINGS: National Research Institute Laboratories. SUBJECTS: Rat aorta and heart, human uterine artery. INTERVENTIONS: Studies of vasoconstriction on isolated vascular rings obtained either from rat aorta or human uterine artery, and of coronary flow, ventricular performance, and heart rhythm on rat hearts using a modified Langendorff heart apparatus. MEASUREMENTS AND MAIN RESULTS: Terlipressin induced a rapid, saturable, and dose-dependent contraction of rat aortas and human uterine arteries. Although the maximal terlipressin-induced vasoconstriction observed on rat arteries was weaker than LVP, or arginine-vasopressin, pharmacologic properties on human arteries, such as full agonism and strong maximal effect (900% of the maximal response obtained with phenylephrine), suggest a high potential of terlipressin to directly vasoconstrict human vessels. Similarly, terlipressin induced a saturable and dose-dependent vasoconstriction of coronary arteries that was reversible and antagonized by selective V1a antagonists. Maximum rates of left ventricle pressure rise (dP/dtmax) and fall (dP/dtmin) decreased both only in proportion to the decrease in coronary flow. CONCLUSIONS: Besides long lasting effect through slow conversion into LVP, terlipressin is a fast acting vasopressor peptide per se that has an impact on coronary circulation and myocardial function.

Cumulative effects of AT1 and AT2 receptor blockade on ischaemia-reperfusion recovery in rat hearts.

Though ischaemia/reperfusion injury induces renin-angiotensin systemic (RAS) activation and increased heart angiotensin production, the effects of blockade of the two main angiotensin II receptors, AT1 and AT2, are not definitively established. Using a Langendorff heart preparation, effects of Valsartan 10(-7)M (AT1 receptor blocker), PD 123319 10(-7)M (AT2 receptor blocker) or both in the presence of a controlled concentration of angiotensin II (10(-8)M) in order to reproduce systemic RAS activation were studied in adult male Wistar rat hearts submitted to ischaemia/reperfusion. Ischaemia/reperfusion impaired both systolic and diastolic function through a no-reflow phenomenon. Presence of a controlled concentration of angiotensin in the perfusate, enough to produce a significant AT1-induced vasoconstriction before ischaemia, has no relevant influence on ischaemia/reperfusion injury. Only blockade of both AT1 and AT2 receptors significantly improved recovery from ischaemia; better ventricle function paralleled better perfusion. The results suggest that blockade of angiotensin II receptors is cumulative since blockade of AT1 and AT2 receptors is more effective than blockade of just one of them.

Hypovolaemia-induced vasodilatation during angiotensin AT1 receptor blockade: role of the AT2 receptor.

AT(1) receptor antagonists may interfere with the haemodynamic determinants of arterial pressure either directly or indirectly through the stimulation of AT(2) receptor provided Ang II is available to interact with them. In order to evaluate the counteracting haemodynamic effect of AT(2) receptor, a prospective, randomized, controlled experimental study was carried out in anaesthetised juvenile pigs. Pigs were randomly assigned to receive placebo (n = 6), valsartan, an AT(1) receptor antagonist (a-AT(1) group; n = 6), or valsartan and PD 123319, an AT(2) receptor antagonist (a-AT(1-2) group; n = 6) after anaesthesia and before hypovolaemia by 20% of the total estimated blood volume. Thirty minutes after bleeding, the mean arterial pressure decreased significantly and similarly in the three groups (25-30%). The placebo group had a significant decrease in cardiac output (CO) without significant change in systemic vascular resistance (SVR). Conversely, in the a-AT(1) group, SVR decreased significantly with a moderate change in CO and addition of the AT(2) antagonist to the AT(1) antagonist (a-AT(1-2) group) did not abolish the lowering in SVR. The results suggest that AT(2) receptor has only a small if any contribution in the vasodilatation observed in the AT(1)-blockade group.

Monitoring weaning from BIVAD Thoratec with peak oxygen consumption.

A biventricular assistance device has been implanted in a young woman for a peripartum cardiac failure. An intended weaning consisted of gradual reloading and exercise training monitored with peak oxygen consumption (VO(2)) and radionuclide-left ventricle ejection fraction. Progressive increase in peak VO(2) during partial assistance occurred more than 2 months, from 10.3 to 19 mL.kg(-1).min(-1). Successful explantation was realized when peak VO(2) exceeded 15 mL.kg(-1).min(-1) and radionuclide-left ventricle ejection fraction was more than 40% during off-pump testing.

Incidence and circumstances of serum creatinine increase after abdominal aortic surgery.

OBJECTIVE: To evaluate the incidence and the circumstances of a moderate increase in serum creatinine early after elective abdominal aortic surgery. DESIGN: Prospective clinical observational study. SETTING: Surgical intensive care unit in a university hospital. PATIENTS: Two hundred and fifteen consecutive adult patients operated on for infra-renal abdominal aortic surgery during 1 year. INTERVENTIONS: A moderate increase in plasma creatinine of 20% from preoperative value (renal dysfunction, RD) was systematically recorded during the first 3 days following surgery. Organ dysfunctions (cardiac, pulmonary, haematological, and neurological) were assessed. MEASUREMENTS AND RESULTS: Forty-three patients (20%) experienced a postoperative RD; six of these required dialysis. RD was associated with other organ dysfunctions in 60.5% patients. Mortality rate was significantly higher for patients who had a RD, than patients without RD (9.3% vs 1.2%, P<0.02). Mean ICU stay of patients with RD was significantly longer (7.9+/-5.6 days vs 5.0+/-1.8 days, P<0.01). However, patients with RD but without other organ dysfunctions had a mortality rate of 0% and did not have a significantly longer stay in ICU than patients without any organ dysfunctions (5.2+/-2.1 days vs 4.6+/-1.2 days, P=0.09). CONCLUSION: Our results suggest that a postoperative 20%-increase in plasma creatinine after abdominal aortic surgery is not rare and occurs frequently with other organ dysfunction.

Ruptured aneurysm of the infrarenal abdominal aorta: impact of age and postoperative complications on mortality.

Between 1985 and 2000, a total of 871 patients underwent surgical treatment for infrarenal abdominal aortic aneurysm (AAA), including 98 (11.2%) presenting with ruptured abdominal aortic aneurysms (RAAA). An optimized operative protocol was used to treat 77 RAAA starting in January 1989. The main features of the optimized protocol are routine use of intraoperative autotransfusion, revascularization by aortoaortic bypass, absence of systemic heparinization, and use of a collagen-impregnated prosthesis. Intraoperative mortality (IOM) was 3.8%. Postoperative mortality at 1 month (POM1) was 25.9% and postoperative mortality at 3 months (POM3) was 33.7%. Heart failure (p <0.001), hemodynamic shock (p <0.001), and hemorrhage (p = 0.04) were the only complications correlated with POM1. Pneumonia (p = 0.01) and sepsis (p = 0.01) were the only complications correlated with POM3. Isolated acute renal insufficiency was not a significant risk factor for postoperative mortality. Using a cutoff of 75 years, there was a significant age-related difference (p = 0.025) for POM1 but not for IOM and POM3. The findings of this study show that optimizing the operative protocol decreases mortality related to RAAA. The main predictor of POM1 was hemodynamic status while the main predictor of POM3 was infection. Isolated acute renal insufficiency was not a risk factor for mortality. Age should not be considered a contraindication for operative treatment.

Incidence, risk factors, and prognosis of a moderate increase in plasma creatinine early after cardiac surgery.

OBJECTIVE: To evaluate the incidence and prognosis of a moderate increase in serum creatinine early after cardiac surgery. DESIGN: Retrospective clinical study. SETTING: Surgical intensive care unit in a university hospital. PATIENTS: Five hundred and ninety-one consecutive adult patients operated on for cardiac surgery during 1 year. INTERVENTIONS: Plasma creatinine was measured systematically before and during the first 3 days after surgery. Comorbid events were assessed as organ dysfunction (cardiac, pulmonary, hematologic, and neurologic), allowing us to calculate for each patient a dysfunction score (0-5). MEASUREMENTS AND MAIN RESULTS: Postoperative plasma creatinine increased by > or =20% in 15.6% of patients; eight of these required dialysis. A 20% increase in plasma creatinine was associated with other organ dysfunction in 79.3% of patients. Overall mortality rate was 2.7% and increased with the dysfunction score (17.7% for a dysfunction score > or =3). Mortality rate was 12.0% for patients who had 20% increased plasma creatinine with other organ dysfunction but was 0% for patients without other organ dysfunction. A logistic regression analysis revealed that the most important prognostic factors of death were cardiac dysfunction (odds ratio, 8.5; 95% confidence interval, 2.2-32.5) and the association of renal dysfunction and hematologic dysfunction (odds ratio = 12.0; 95% confidence interval, 3.9-37.2). Mean intensive care unit stay of patients with increased plasma creatinine was significantly longer (8.1 +/- 5.6 vs. 4.3 +/- 1.4 days, p <.01) and increased significantly with the dysfunction score (p <.01). Patients with isolated increased plasma creatinine had a significantly longer stay in the intensive care unit than patients without any organ dysfunction (4.6 +/- 1.4 vs. 3.9 +/- 0.9, p <.01). CONCLUSION: Our results suggest that a postoperative 20% increase in plasma creatinine after cardiac surgery is not rare and has a significant impact on postoperative outcome, mainly when multiple organ dysfunction occurs. Any preoperative reduced renal reserve or perioperative renal ischemia increases the renal risk.