Influence of Diltiazem on Cardiovascular Function and Coronary Hemodynamics during Isoflurane Anesthesia in the Dog

Kapur, Patricia A.; Campos, Javier H.

doi:10.1213/00000539-198601000-00013

Anesthesia & Analgesia

1986

DOI: 10.1213/00000539-198601000-00013

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Influence of Diltiazem on Cardiovascular Function and Coronary Hemodynamics during Isoflurane Anesthesia in the Dog

Patricia A. Kapur

Javier H. Campos

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1986

1991

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Cited by 16 publications

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“…Because combined cardiovascular depressant effects may limit the use of verapamil in the presence of inhalation anesthestics (7), diltiazem may be a potential alternative if therapeutically indicated during inhalation anesthesia. Previous work in our laboratory has demonstrated that clinically relevant plasma levels of diltiazem are generally well-tolerated during 1.5% end-tidal isoflurane anesthesia in a canine model (8). Plasma level-related prolongation of the PR interval of the electrocardiogram and mild depression of left ventricular dPidt were the major findings.…”

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confidence: 78%

“…Temperature was maintained between 38-39°C with a warming blanket and a heat lamp. The experimental preparation was identical to that in a previous study with isoflurane (8). Catheters were placed in an external jugular vein for drug administration and infusion of 0.9% NaCl at 5 rnl.kgP'.hr-', in a femoral artery for blood samples and measurement of phasic and mean arterial blood pressure (MAP), and in a pulmonary artery for measurement of right atrial (RA) and pulmonary artery occluded (PAO) pressures and for sampling of mixed venous blood.…”

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confidence: 99%

“…A 7F woven Dacron coronary sinus thermodilu tion catheter (Model CCS-7U-90B, Webster Laboratories, Inc., Altadena, California) was passed into the coronary sinus under fluoroscopic control via an external jugular vein to measure coronary sinus (CS) pressures and blood flow and to obtain CS blood samples. Its position was confirmed every 30 min as in the prior study (8). Coronary sinus blood flow (Qcs) was measured in duplicate by means of a technique adapted from Ganz et al (12), as detailed previously (8).…”

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confidence: 99%

“…Its position was confirmed every 30 min as in the prior study (8). Coronary sinus blood flow (Qcs) was measured in duplicate by means of a technique adapted from Ganz et al (12), as detailed previously (8).…”

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confidence: 99%

“…In addition the ECG was intermittently recorded at fast paper speed (100 mm/s) for measurement of PR intervals. Inhaled and exhaled gases were analyzed by a mass spectrometer and exhaled gas volume was measured with a modified electronic volume displacement spirometer (8). Intermittent samples were simultaneously taken of arterial, mixed venous, and CS blood for blood gas tensions, pH, and blood oxygen content.…”

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Plasma Diltiazem Levels, Cardiovascular Function, and Coronary Hemodynamics during Enflurane Anesthesia in the Dog

Kapur

Campos

Buchea

1986

Anesthesia & Analgesia

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KAPUR PA, CAMPOS JH, BUCHEA OC. Plasma diltjazem levels, cardiovascular function, and coronary hemodynamics during enflurane anesthesia in the dog. Anesth Analg 1986;65:918-24.Diltiazein 7ons ndininistered to dogs by a n intraueiious illfiisiori protocol, which resulted in plasma levels of 71 ? 6 ( I i = 7 ) , 139 ? 9 ( n = 7), 353 i 33 ( n = l o ) , and 1064 ? 143 (11 = 6) ng/ml, to ezialunte the effects of diltiazetn on i-nrrfiouasculur functioii mid coronar>y heinodynainics in the prescnce of mesthetic concentratioiis of enfluranc. An additional xroup of six dogs receizied enf7iirane only. The only c h a n p olwrued zilith eiiflurnne alone were 17 decrease in Icft z~entricular (LV) dPldt, cardinc index (Cl), nnd coronariy blood f7ozi1 60 inin after the haselirie m m i i r m e n t s were rnadr. I n all of fhe diltiazem groups, p l a s m leuel-related donga at ion of tkc PR interval of the elecfrocnrdiogrnrn iias observed, iiiith developinent of second degree henrt block and jrriictionnl rhythms in animals at the tziio hiRher plasma Jc~w/s. Mean nrterial pressure and LV dPidt decreased nt the two higher diltiazein plusinn leuels after 30 inin (if itrfusion, nnd three of six dogs in the highest group had to be dropped froin the study because of severe hypotension. The cardiac index ZORS no different from enflurane alone with the three lower plasma diltiazem levels. No changes were obserued in coronary sinus blood flow, coronary vascular resistnnce, inyocardinl oxygen uptake, or myocardial lactate extraction. Circulating norepinephrine levels were elevated in the tzoo higher diltiazein groups. In the presence of anesthetic coticentrations of enflurane, over the range of plasma diltiazein leziels investigated in this study, conduction effects w r e proriiinent and decreases in left ventricular performance and hlood pressure occurred as plasma diltiazem levels iiicreased. No untoward effects on global myocardial metnholisin zuere detected at plasma levels less than 500 ngi nil. However, the occurrence of circulatory collapse in half of the nninials at the highest plasma levels prevented evaluation of nietabolic effects of high levels of diltiazem during enflurane anesthesia.Diltiazem has a spectrum of clinical usefulness similar to that of verapamil (1-6). Because combined cardiovascular depressant effects may limit the use of verapamil in the presence of inhalation anesthestics (7), diltiazem may be a potential alternative if therapeutically indicated during inhalation anesthesia. Previous work in our laboratory has demonstrated that clinically relevant plasma levels of diltiazem are generally well-tolerated during 1.5% end-tidal isoflurane anesthesia in a canine model (8). Plasma level-related prolongation of the PR interval of the electrocardiogram and mild depression of left ventricular dPidt were the major findings. No alterations in global left ventricular oxygen consumption or coronary hemodynamics were noted. However, the previous study was limited to isoflurane and to plasma levels of diltiazem less than 60...

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confidence: 78%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Plasma Diltiazem Levels, Cardiovascular Function, and Coronary Hemodynamics during Enflurane Anesthesia in the Dog

Kapur

Campos

Buchea

1986

Anesthesia & Analgesia

Self Cite

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Combined negative inotropic effects of calcium entry blockers and isoflurane on canine isolated heart muscles

Nakata

Kemmotsu

1991

J Anesth

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The combined negative inotropic effects of isoflurane and calcium entry blockers (verapamil, diltiazem, nifedipine, nicardipine) were studied utilizing isolated heart preparations of ventricular muscles from dogs. All of these calcium entry blockers exerted dose-dependent decreases in maximal velocity of shortening (Vmax), maximal developed isometric force (Fm), and the maximal first derivative of Fm (maximal dF/dt). Dose-dependent decreases of these variables of muscle mechanics were augmented in isoflurane-depressed myocardium. At equimolar concentrations, direct myocardial depression was demonstrated in the following order of severity: nifedipine > diltiazem = verapamil > nicardipine. Percent depressions of Vmax, Fm and maximal dF/dt were significantly greater in muscles when calcium entry blockers were combined with 1MAC isoflurane than in muscles of calcium entry blockers alone. These data suggest that the negative inotropic effects of verapamil, diltiazem, nifedipine, and nicardipine were potentiated by isoflurane.

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Interaction between diltiazem and halothane or enflurane in the canine blood-perfused papillary muscle and sinoatrial node preparations cross-circulated by chronically instrumented conscious donor dog

1988

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Interaction of cardiovascular effects of diltiazem with those of halothane or enflurane was estimated in the canine isolated papillary muscle and sinoatrial node preparations perfused by arterial blood of the chronically instrumented conscious and halothane- or enflurane-anesthetized donor dog, into which diltiazem was infused i.v. at a rate of 20 micro g/kg/min for 60 min. One hour after diltiazem infusion, in the conscious donor dog, mean arterial pressure (MAP) and heart rate (DHR) were decreased to 84 +/- 3 and 84 +/- 2% and PQ interval (PQ) was prolonged to 148 +/- 5%, while in the isolated preparations, developed tension (DT) of the papillary muscle and sinoatrial rate (SAR) were decreased to 68 +/- 3 and 74 +/- 3% and blood flow (BF) was increased to 155 +/- 5% (n = 10). On the other hand, halothane (0.8%) anesthesia per se decreased MAP, DHR, DT and SAR to 89 +/- 8, 84 +/- 3, 79 +/- 3 and 89 +/- 5% (n = 7) of each basal value in conscious state 20 min after the inhalation. During halothane anesthesia, the same dose of diltiazem infused decreased MAP to 74 +/- 4 (n = 7), DHR to 66 +/- 4 (n = 6), DT to 62 +/- 7 (n = 7) and SAR to 69 +/- 1% (n = 3) of each value suppressed by halothane itself. Meanwhile, enflurane (1.7%) anesthesia itself decreased MAP, DHR, DT and SAR to 81 +/- 3, 85 +/- 2, 81 +/- 2 and 88 +/- 2% (n = 10) of each basal value in conscious state 30 min after enflurane inhalation. During enflurane anesthesia diltiazem decreased MAP to 74 +/- 3 (n = 10), DHR to 67 +/- 3 (n = 8), DT to 45 +/- 5 (n = 10) and SAR to 74 +/- 6% (n = 3) of each value under enflurane anesthesia alone. PQ interval of the donor dog heart was prolonged by halothane alone to 111 +/- 5% (n = 7) and by enflurane alone to 110 +/- 2% (n = 10) of the value before each anesthesia, and then diltiazem prolonged PQ interval to 160 +/- 8% (n = 6) and 174 +/- 10% (n = 8) of each value suppressed by the anesthetic itself during halothane- or enflurane-anesthesia, respectively. The second degree AV conduction block was induced in 1 of 7 halothane- and in 2 of 10 enflurane-anesthetized donor dogs, respectively. The sinus arrest was induced by diltiazem in 4 of 7 sinoatrial node preparations under halothane and in 7 of 10 ones during enflurane anesthesia. Moreover, plasma concentration of diltiazem 60 min after the start of infusion was 556 +/- 121 ng/ml in conscious dogs and tended to increase to 752 +/- 101 ng/ml in enflurane anesthetized donor dogs (n = 4), but there was no significant difference between two values (0.05 < P < 0.1). These results indicate that effects of diltiazem could be potentiated during halothane or enflurane anesthesia by elimination of compensatory reflex noted in conscious state, and that the negative inotropic effect of diltiazem was enhanced by enflurane anesthesia due to unknown mechanisms which probably include a slight but insignificant increase in plasma concentration.

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Influence of Diltiazem on Cardiovascular Function and Coronary Hemodynamics during Isoflurane Anesthesia in the Dog

Cited by 16 publications

References 0 publications

Plasma Diltiazem Levels, Cardiovascular Function, and Coronary Hemodynamics during Enflurane Anesthesia in the Dog

Plasma Diltiazem Levels, Cardiovascular Function, and Coronary Hemodynamics during Enflurane Anesthesia in the Dog

Combined negative inotropic effects of calcium entry blockers and isoflurane on canine isolated heart muscles

Interaction between diltiazem and halothane or enflurane in the canine blood-perfused papillary muscle and sinoatrial node preparations cross-circulated by chronically instrumented conscious donor dog

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