Cardiovascular responses to experimental infra-renal aortic cross-clamping. Modulating effects of isoflurane, sodium nitroprusside and milrinone

Coiivrivlil 0Achi Aiiacstlirsiol Scniid 1996

ACTA ANAESTHESIOLOGICA SCANDINAVICA

ISSN 0001-5172

Cardiovascular responses to experimental infra-renal aortic cross-clamping. Modulating effects of isoflurane, sodium nitroprusside and milrinone H. SEEMAN-LODDING', 8. BIBER3, J. MARTNER4, J.

PONTEN'

and 0.WINSO

Dqwtrtrcrrts of Ariesfhesiology, 'Ostra arid 'Snhlgrens University Hospitnls, Gothenburg, 3Uti~edLlniversity Hospital, Urirea' , nnd 'Miilridal Hospital, Mdridal, Sweden

Background: Pharmacological control of blood pressure is usually indicated during aortic cross-clamping (AXC). The aim of this study was to analyze the modulation by isoflurane (ISO), sodium nitroprusside (SNP) and milrinone (MIL) of the systemic circulatory responses to a standardized infrarenal AXC. Methods: Chloralose-anaesthetized pigs were exposed to AXC at control (no vasoactive drugs) and during the administration of each of the drugs. Results: During control, AXC increased mean arterial pressure (MAP, 17M%) and systemic vascular resistance (SVR, 27f7%), but induced no significant changes in cardiac output (CO), heart rate (HR), pulmonary arterial pressures, pulmonary vascular resistance or central venous pressure. Low-dose IS0 (0.7%) and investigated doses of SNP and MIL did not significantly alter this response. High-dose IS0 (1.4%:attenuated the AXC-induced increase in SVR, but not in MAP. All drugs decreased non-clamp MAP levels. Therefore, with lowdose IS0 and with SNP or MIL, peak MAP during AXC was

not significantly different from control non-clamp levels (i.e. prior to pharmacological or surgical interventions). Highdose IS0 was associated with a MAP during AXC that was below control non-clamp levels. Conclusions:The objective that during AXC MAP should not exceed control non-clamp levels was achieveable by KO, SNP or MIL. The modulating actions of the drugs on MAP during AXC were exerted mainly through reductions in non-clamp levels. This systemic hypotension was associated with decreased CO and SVR during ISO, and with decreased SVR and increased HR during SNP and MIL. Attenuation of the AXCinduced increase in SVR was produced only by 1.4%ISO.

haemodynamic consequences of abdominal aortic cross-clamping (AXC), a prerequisite for AAA (abdominal aortic ancurysm) surgery, have been reported in experimental and clinical studies. In the circulation proximal to the clamp , AXC is usually associated with increases in arterial blood pressure and systemic vascular resistance and moderate reductions in stroke volume and cardiac output (1-4). The effects of AXC on pulmonary arterial occlusion pressure and central venous pressure seem to depend on whether ischaemic heart disease is present or not (5). Pharmacological interventions to control proximal blood pressure augmentations are usually indicated during AAA surgery. The complex cardiovascular response producing the blood pressure increase during AXC can, from a patho-physiological point of

view, be countered by drugs representing different pharmacological principles. Pure vasodilators, such as sodium nitroprusside (SNP) (6),or agents that besides being vasodilators also possess cardiac depressant actions, such as halogenated inhalational anaesthetics (7, 8), are usually chosen for this purpose. Phosphodiesterase I11 (PDE) inhibitors represent a different pharmacological approach (9-11). A potential advantage of this kind of therapy is that drug-induced vasodilation could be associated with inotropic support of cardiac performance during the increases in pre-and afterload that are typically produced by AXC. This study was designed to define the circulatory response following an infra-renal AXC, to analyze cardiovascular adjustments underlying this response, to assess the respective efficacy of ISO, SNP

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Rrceiiird 4 /uiiuary, accepted for putilicutioit 31 August 1995

Key words: Aortic cross-clamping; hemodynamic responses; isoflurane; milrinone; sodium nitroprusside; pig. 0Arfa Aiiursfhesiologica Scandiiiar~ica40 (1996)

Haemodynamics and aortic cross-clamping

and MIL to control proximal blood pressure in this situation and to elucidate the cardiovascular reactions that are involved in such pharmacological modulations.

Material and methods Sixteen pigs (9 females and 7 males), approximately 3 months old, with a mean weight of 32.823.0 kg (30 -38 kg) were, after approval of the Goteborg University Animal Experiment Ethics Committee, included in the study. Thc animals fasted overnight. Anaesthesia was induced with 1000 mg ketamine i.m. and maintained by i.v chloralose (100 mg .kg-'+ 45-60 mg.kg-'.h-'). No muscle relaxants were used. Orotracheal intubation o r tracheostomy was carried out to allow controlled ventilation (UR 70, Dameca, Sweden) with oxygen in air (50% 0,) at a frequency of 20.min-'. Ventilation was adjusted to normocapnia as indicated by end-tidal CO, levels (Normocap, Datex, Finland) and intermittent arterial blood gas analyses (ABL-2 autoanalyser, Radiometer, Denmark). Thv animals received continuous infusions of Ringer's acetate 10 ml.kg-l.h-' and dextran 70 (Macrodex w, Pharmacia, Sweden) 2 ml .kg-l. h-' throughout the experiments. Core temperature was kept between 37-38°C using an infrared lamp and a heating pad. Thc external and internal jugular veins and the carotid 'jrtery were exposed through a right-sided neck dissection. A flow-directed catheter was introduced into the pulmonary artery to record mean pulmonary arter!. pressure (MPAP), pulmonary artery occlusion pressure (PAOP) and core temperature. Central venous pressure (CVP) was measured via a proximal sideport of the pulmonary artery catheter. Cardiac output (CO) was measured by the thermodilution technique, using 5 ml iced 0.9% NaCl as indicator (Edward's Cardiac Output Computer, Baxter Edward's Critical Care, USA). Cardiac output data are presented as means of three consecutive measurements Mean aortic arterial pressures were recorded both proximally (MAP) and distally (DMAP) to the site ot a n abdominal aortic occlusion snare (see below) by catheters in the proximal aorta (via the carotid ,lrtery) and the distal aorta (via the right femoral arterv), respectively. Heart rate (HR) was obtained from the proximal aortic pressure tracing. Recordings were made on a Grass 7D polygraph (Grass Instrument\ CO, USA). To monitor urine production, urethral catheterization was performed in female ani-

mals, while males underwent an open cystostomy. The infra-renal part of the abdominal aorta was exposed by a long midline abdominal incision. To achieve intermittent aortic cross-clamping (AXC), a 1 cm wide cotton snare was pulled around the aorta 4 cm caudal to the renal arteries and secured through a 15 cm long plastic tube (00.5 cm ). The incision was then closed around the plastic tube and aortic cross-clamping could be achieved by advancing the tube along the cotton snare, thus tightening the snare around the vessel. According to the experimental protocol (see below), the snare was intermittently tightened to obtain a complete occlusion of the aorta. We monitored DMAP throughout the experiments to allow comparisons between different stages of the study and to ascertain that the aorta was unobstructed between clamping procedures.

Experimental protocol Animals were randomly divided into two groups. All animals in group 1 (n=10) were administered two doses of, respectively, IS0 (0.7% and 1.4%), SNP (5 pLg.kg-'.min-l and 10 pg.kg-'.min-' ) and MIL (50 pg.kg-'+5 p8.kg-l. min-' and 100 pg.kg-'+lO Fg.kg-'.min-'). The initial drug was either IS0 or SNP in a randomized fashion. MIL (bolus and continuous infusion) was consistently administered as the last drug due to its relatively long half-life in plasma (lo), which precluded a complete randomization of the protocol. Also, for the same reason, the low MIL dose was always given before the high MIL dose. The experimental protocol is depicted in Fig. 1.The end-tidal concentrations of IS0 were continuously monitored by a gas analyzer (Anemon,

EXPERIMENTAL PROTOCOL

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409

H. Seeman-Lodding et al.

Cardiomedic AB, Sweden) and adjusted to 0.7% and 1.40/0, respectively. These doses of IS0 correspond to 0.5 and 1.0 MAC in the pig when given as the sole anesthetic (12): To evaluate whether any time-related effects on the proximal pressor response to AXC or carry-over drug effects occured in group I, animals in group 2 (abbreviated experiments, n=6) were investigated according to an abbreviated protocol comprising only a control stage and the subsequent administration of MIL, using the same dose regimen as in group I. In both groups, a stabilization period of at least 20 min was allowed to elapse after changes in drugs or doses. The registration sequences for control stages (no drugs) and for each drug dose, included measurements of haemodynamic parameters a) immediately prior to AXC, b) at the end of a 5-min-AXC period and c) 5 min following the discontinuation of AXC (see Fig. 2). We calculated systemic vascular resistance (SVR) as (MAP-CVP)/CO and pulmonary vascular resistance (PVR) as (MPAP-PAOP)/CO.

Statistical analyses For analyses of the primary effects of ISO, SNP or MIL and of the modulatory effects of these drugs on the AXC-induced haemodynamic responses, analyses of variance (ANOVA; Systat 5.02 for Windows

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software, Systat Inc., Evanston, IL, U.S.A.) was used. When indicated (P