Summary: This study was undertaken in dogs to investigate the effects of nicardipine (NCR)- and prostaglandin E1 (PGE1)- induced hypotension on left ventricular myocardial function, and on coronary hemodynamics in the presence of a partially obstructed left coronary artery. A stenosis of left circumflex coronary artery (LCX) was induced to reduce LCX blood flow by 20%. Mean arterial pressure (MAP) was lowered by infusion of NCR or PGE1 to 80% and 60% of the control. Heart rate, cardiac index, left ventricular dp/dt max, myocardial oxygen extraction ratio, inner/outer blood flow ratio and myocardial lactate extraction ratio showed no significant change at either 80%- or 60%-MAP during infusion of either drug. PGE1 -induced hypotension reduced left ventricular end-diastolic pressure at both 80%- and 60%-MAP. The results indicate that the moderate hypotension induced by NCR or PGE1 does not exert either myocardial depression or adverse effects on the myocardial oxygen supply-demand relationship in the presence of a critical coronary stenosis

Miyako Masahiko

Miyako, Masahiko

Nagasaki university's Academic Output SITE

Effects of Nicardipine and Prostaglandin E1 on Coronary Hemodynamics in Dogs with Coronary Artery Stenosis.

Summary: This study was undertaken in dogs to investigate the effects of nicardipine (NCR)- and prostaglandin E1 (PGE1)- induced hypotension on left ventricular myocardial function, and on coronary hemodynamics in the presence of a partially obstructed left coronary artery. A stenosis of left circumflex coronary artery (LCX) was induced to reduce LCX blood flow by 20%. Mean arterial pressure (MAP) was lowered by infusion of NCR or PGE1 to 80% and 60% of the control. Heart rate, cardiac index, left ventricular dp/dt max, myocardial oxygen extraction ratio, inner/outer blood flow ratio and myocardial lactate extraction ratio showed no significant change at either 80%- or 60%-MAP during infusion of either drug. PGE1 -induced hypotension reduced left ventricular end-diastolic pressure at both 80%- and 60%-MAP. The results indicate that the moderate hypotension induced by NCR or PGE1 does not exert either myocardial depression or adverse effects on the myocardial oxygen supply-demand relationship in the presence of a critical coronary stenosis.Acta medica Nagasakiensia. 1993, 38(2-4), p.232-236departmental bulletin pape

Nagasaki University's Academic Output SITE: NAOSITE

Acta Med. Nagasaki 38:232 - 236Effects of Nicardipine and Prostaglandin E1 on Coronary Hemodynamics in Dogs with Coronary Artery Stenosis.Masahiko MiyakoDepartment of Anesthesiology, Nagasaki University School of Medicine, 1-7-1, Sakamoto, Nagasaki 852, JapanSummary: This study was undertaken in dogs to investigate the effects of nicardipine (NCR)- and prostaglandin E1 (PGE1)- induced hypotension on left ventricular myocardial function, and on coronary hemodynamics in the presence of a partially obstructed left coronary artery. A stenosis of left circumflex coronary artery (LCX) was induced to reduce LCX blood flow by 20%. Mean arterial pressure (MAP) was lowered by infusion of NCR or PGE1 to 80% and 60% of the control. Heart rate, cardiac index, left ventricular dp/dt max, myocardial oxygen extraction ratio, inner/outer blood flow ratio and myocardial lactate extraction ratio showed no significant change at either 80%- or 60%-MAP during infusion of either drug. PGE1 -induced hypotension reduced left ventricular end-diastolic pressure at both 80%- and 60%-MAP. The results indicate that the moderate hypotension induced by NCR or PGE1 does not exert either myocardial depression or adverse effects on the myocardial oxygen supply-demand relationship in the presence of a critical coronary stenosis.Introduction Deliberate hypotension is an anesthetic technique to de-crease blood loss during surgery and to provide a dry field for the surgeon."'-" Intravenous nicardipine (NCR)4.5' 6) and prostaglandin E, (PGE,)''8.9' have been introduced in recent years to control blood pressure during clinical anesthesia, and have proved to be useful for deliberate hypotension.   NCR lowers blood pressure resulting from vasodilation due to inhibition of calcium influx into the vascular smooth muscle. NCR mainly dilates resistance vesseles and also has an effect to increase coronary blood flow.'°' PGE, exerts direct relaxing action on the vascular smooth muscle and causes hypotension. PGE, also has been shown to cause coronary vasodilation and reduction of both preload and afterload of the left ventricle.". 12. 13)  The blood flow to ischemic myocardium depends on coronary perfusion pressure, and it is risky to lower arterial pressure in the patients with ischemic heart disease."' Although NCR and PGE, are considered to be beneficial for the ischemic heart, it is not clear how these compounds affect the heart with critical coronary-artery stenosis14' when administered to lower arterial blood pressure rapidly during general anesthesia. The present study was designed to investigate the effects of NCR- and PGE,-induced hypotension on left ventricular myocardial function, and on coronary hemodynamics in the presence of partially obstructed left coronary circulation.Materials and Methods. Surgical preparation Sixteen mongrel dogs of either sex, weighing 11.4 to 15.6 (mean 13.1) kg were used in this study. Anesthesia was induced with 30mg/kg of sodium pentobarbital i. v., and maintained with continuous infusion of sodium pentobar-bital, 1 mg/kg/min, pancuronium chloride, i. v. appropri-ately, and inhalation of 50% N2O in O2. The animals were intubated with a cuffed endotracheal tube and ventilated mechanically with air at a tidal volume of 15ml/kg. End-tidal CO, concentration was measured continuously with an infrared CO2 analyzer (Datex, Helsinki) and maintained at levels of 35-40mmHg by adjusting the respiratory rate. An infrared heating lamp and a circulating water blanket were used to maintain the esophageal temperature between 37-38.5C. Arterial blood gas analysis and measurement of serum electrolytes were carried out frequently to maintain pH of 7.35 to 7.45, serum Na of 135 to 155mEq/1 and serum K of 3.7 to 5.3mEq/1. Active intervention was not necessary to maintain these ranges except for adjusting pH with 7% NaHCO3 solution in some animals.   In all dogs, catheters were inserted into the femoral vein, into the abdominal aorta via the left femoral artery (Fig. 1). Normal saline was administered at a rate of 4-6ml/kg/hr into the femoral vein into which NCR and PGE, were also administered. Intraarterial pressure was monitored via the abdominal aorta. The chest was opened through the sixth left intercostal space, and the heart was suspended in a pericardial cradle. Precalibrated electromagnetic flow probes (Nihon Kohden, Japan) of appropriate sizes to ensure a snug fit were placed around the ascending aorta, the left circumflex coronary artery (LCX) approximately 1-2cm distal to its origin, and the left anterior descending coronary artery (LAD) distal to its first large diagonalFig. 1. Schematic diagram of the experimental preparationbranch. The flow probes were connected to flowmeters (Nihon Kohden, Japan). A catheter was inserted into the left ventricle via the cardiac apex to measure the left ventricular pressure. A damping device (Accudynamics Sorenson Research, Salt Lake City) was used to get an appropriate damping of the pressure wave. Myocardial blood flow was measured with the hydrogen gas clearance method using platinum tissue electrodes (200um in diam-eter) at both the outer layers (2-3mm in depth) and the inner layers (8-9mm in depth). Experimental protocol At the end of the surgical preparation, at least 30min were allowed for stabilization. After control readings (presten-osis value) had been obtained, a stenosis of LCX was induced using a stainless steel screw type mechanical occluder placed immediately distal to the flow probes. The stenosis was defined as the constriction necessary to reduce LCX blood flow by 20%. About 30min was allowed after inducing stenosis for the reactive hyperemia to disappear and for hemodynamic stabilization, and the second readings (basal value) were obtained.  Then the dogs were randomly divided into two groups to recieve NCR or PGE,. Both NCR and PGE, were dissolved in normal saline, and NCR was used as a 0.02% solution, PGE, as a 0.0025% solution. NCR and PGE, was infused at a dose which caused decrease in MAP to 80% of the basal value. After maintenance of stable MAP for 30min, the third readings (80% MAP value) were obtained. The dose of NCR or PGE, was then increased to cause decrease in MAP to 60% of the basal value. After maintenance ofstable MAP for 30min, the fourth readings (60% MAP value) were obtained. The hemodynamic data were calcu-lated by the formula shown in Table 1.Table 1. Hemodynamic Formulas -CI = CO/BSA  •TPR = MAP x 79.92/CO  •I/O RATIO = MBFI/MBFO  •OER = (Ca02-CcsO2)/Ca02 x 100  •LER = (LaA-LaCS)/LaA x 100 ABBREVIATIONS CI: cardiac index CO: cardiac output BSA: = body surface area 0.112 x (weight:kg)' TPR: total peripheral resistance MBFI: myocardial blood flow through the inner layer MBFO: myocardial blood flow through the outer layer OER: myocardial oxygen extraction ratio Ca02: arterial oxygen content CcsO2: coronary sinus oxygen content LER: myocardial lactate extraction ratio LaA: arterial lactate content LaCS: coronary sinus lactate contentStatistics For statistical analysis, paired t-test was used for compar-ison between the basal value and the pre-stenosis value and between 80%-MAP or 60%-MAP value and the basal value. Non-paired t-test was used for comparison between groups of NCR and PGE,. All results are expressed as mean ± SEM. A P value less than 0.05 was considered statistically significant.Results The mean doses to maintain 80%- and 60%-MAP were 5.2 ± 0.54 and 15.6 ± 1.58,ug/kg/min for NCR, and 0.63 ± 0.04 and 1.90 ± 0n l3,ug/kg/min for PGE,.   Heart rate, cardiac index, left ventricular dp/dt max showed no significant change at 80%- or 60%-MAP in either drug (Table 2 and 3). Total peripheral resistance exhibited significant decrease dose-dependently at 80%-and 60%-MAP in both drugs. Left ventricular end-diastolic pressure showed a significant decrease at 80%- and 60%-MAP in PGE,, but showed no change in NCR. The blood flow in the left anterior descending coronary artery (LADF), which was a non-stenosed vessel, showed no significant change at 80%- or 60%-MAP in either drug. Myocardial blood flow at the inner (MBFI) and outer layers (MBFO) of the left circumflex coronary artery stenosis region showed no significant change at 80%- or 60%-MAP in either drug. There was a significant increase in inner/outer blood flow (I/0) ratio at 60%-MAP in NCR (Fig. 2). Myocardial oxygen extraction ratio (OER) and Myocardial lactate extraction ratio (LER) showed no significant change at 80%- or 60%-MAP in either drug (Fig. 3 and 4).Table 2. Effects of Nicardipine-Induced Hypotension on Systemic and Coronary Hemodynamics (Mean ± SEM; N = 8)                                                                       Stenosis         Variables Prestenosis                                                   Basal 80%-MAP 60%-MAP  HR (bpm) 143 ± 3 141 ± 2 140±4 136±5  MAP (mmHg) 134 ± 4 128 ± 5* 106 ± 6*,** 80 ± 6*,**  CI (1/min/m2) 2.57 ± 0.16 2.53 ± 0.15 2.74 ± 0.20 2.78 ± 0.13  LVdp/dtmax (mmHg/sec) 3600 ± 133 3314 ± 175* 3371 ± 175 2951 ± 305  LVEDP (mmHg) 3.38 ± 0.45 3.88 ± 0.55 3.50 ± 0.64 3.75 ± 0.69  TPR (dynes-sec/em') 7055 ± 470 6840 ± 476 5306 ± 505*,** 3854 ± 348*,**  LCXF (ml/min) 44.0 ± 2.9 33.8 ± 3.1* 33.0 ± 2.7* 31.8 ± 2.9*  LADF (ml/min) 11.6 ± 1.1 13.6 ± 1.0* 13.1 ± 1.5 13.6 ± 2.0  MBFI (ml/100g/min) 86.2 ± 2.6 78.2 ± 3.9* 83.7 ± 5.7 80.6 ± 10.4  MBFO (ml/100g/min) 70.5 ± 3.9 58.6 ± 5.0* 61.1 ± 6.7 55.0 ± 9.1  I/O ratio 1.23 ± 0.04 1.37 ± 0.07* 1.41 ± 0.05* 1.51 ± 0.05*  OER (%) 63.3 ± 6.5 63.0 ± 4.4 56.2 ± 5.3 55.1 ± 6.9  LER (%) 34.6 ± 7.2 25.7 ± 5.9 27.4 ± 4.1 23.7 ± 5.1 * P < 0.05 vs pre-stenosis value, * * P < 0.05 vs basal valueTable 3. Effects of Prostaglandin E,-Induced Hypotension on Systemic and Coronary Hemodynamics (Mean ± SEM; N = 8)                                                                       Stenosis         Variables Prestenosis                                                 Basal 80%-MAP 60%-MAP  HR (bpm) 141 ± 2 141 ±2 144 ± 4 144 ± 4  MAP (mmHg) 141 ± 6 130 ± 7* 111 ± 6*,** 87 ± 4*,**  CI (1/min/m2) 2.51 ± 0.16 2.53 ± 0.17 2.77 ± 0.17* 2.72 ± 0.23  LVdp/dtmax (mmHg/see) 3656 ± 93 3456 ± 170 3455 ± 98 3279 ± 150*  LVEDP (mmHg) 3.38 ± 0.67 4.25 ± 0.85* 3.38 ± 0.83** 3.25 ± 0.69**  TPR (dynes-sec/em') 7264 ± 209 6664 ± 297* 5208 ± 246*,** 4264 ± 345*,**  LCXF (ml/min) 42.9 ± 2.9 34.0 ± 2.5* 32.5 ± 2.2* 29.0 ± 2.0*,**  LADF (ml/min) 10.5 ± 1.1 12.9 ± 1.1 13.8 ± 0.9* 12.4 ± 1.0*  MBFI (ml/lOOg/min) 86.9 ± 2.0 86.4 ± 4.9 89.2 ± 2.8 83.7 ± 4.6  MBFO (ml/100g/min) 67.3 ± 2.7 66.0 ± 4.0 65.5 ± 2.3 63.1 ± 2.3  I/O ratio 1.30 ± 0.07 1.32 ± 0.05 1.37 ± 0.04 1.33 ± 0.06  OER (%) 66.1 ± 2.7 69.0 ± 4.9 65.1 ± 1.7 65.3 ± 3.8  LER (%) 36.8 ± 4.1 25.1 ± 4.6* 22.8±3.5* 25.6 ± 5.2* * P < 0.05 vs pre-stenosis value, ** P < 0.05 vs basal valueFig. 2. Effects of nicardipine- and prostaglandin E,-induced hypotension on the inner/outer layer (I/O) ratio of myocardial blood flow (mean ± SEM; n = 8 for each value) *P < 0.05 VS Pre-stenosis value, ***P < 0.05 between the groupsFig. 3. Effects of nicardipine- and prostaglandin E,-induced hypotension on the myocardial oxygen extraction ratio (OER) (mean ± SEM; n = 8 for each value)Fig. 4. Effects of nicardipine- and prostaglandin E,-induced hypotension on the myocardial lactate extraction ratio (LER) (mean ± SEM; n = 8 for each value) * P < 0.05 VS Pre-stenosis valueDiscussion A model of critical coronary artery stenosis'°' was made in the present experiment. Under this condition, the coronary artery distal to stenosis was dilated maximally and the autoregulation was lost. Thus, the coronary blood flow would depend on the coronary perfusion pressure."' In-deed, in the present experiment, the blood flow of the stenosed artery decreased in proportion as the arterial pressure lowered. It is known that the aggravation of myocardial oxygen demand-supply relationship develops initially at the inner leyers and that the cellular necrosis during ischemia begins from the inner layers."' In the normal heart, the inner layers of the ventricle have a higher blood flow per unit weight than the outer layers, and the oxygen consumption of the inner layers is also higher than that of the outer layers."' In the heart with coronary artery stenosis, the myocardial blood flow at the inner layers is characteristically underperfused due to the low coronary pressure caused by stenosis.'a' In the present experiment, there was no significant difference in the myocardial blood flow at the inner layers and myocardial blood flow at the outer layers at the stenosed area at 80%- or 60%-MAP in either NCR or PGE,. It has been reported that the I/O ratio in the left ventricle of dogs are between 1.0 to 1.3 in the absence of narrowed coronary artery."' in the persent results, the I/O ratio was more than 1.0 at 80%- and 60%-MAP during both drugs, suggesting that there would be no insufficient perfusion in the inner layers of the ventricle. It is known that when myocardial oxygen demand in-creases, the coronary artery blood flow also increases to cope with it, but myocardial oxygen extraction ratio does not change. In the present study, the myocardial oxygen extraction ratio did not change at 80%- or 60%-MAP during either drug, indicating that there might be coronary artery dilation, which were not due to an increase in the myocardial oxygen consumption. Myocardial lactate ex-traction ratio is considered as an index for myocardial ischemia.20' It has been reported that the myocardial lactate extraction ratio less than 10% would indicate myocardial ischemia.21' In the present results, the myocardial lactate extraction ratio was more than 10% at both 80%- and 60%-MAP during both drugs, and there was no significant difference between the two drugs.  Heart rate is an important factor to determine myocardial ischemic disorder,") and the local myocardial contractility might be effected when heart rate increases. In the present study, heart rate remained almost constant, and seemed not to play a role in the change of myocardial oxygen demand-supply relationship. CI and LVdp/dt max showed no signif-icant change at 80%- and 60%-MAP in either drug, indi-cating that there was no myocardial depression during the each drug-induced hypotension.   In conclusion, the moderate hypotension induced by NCR or PGE, does not exert either myocardial depression or adverse effects on the myocardial oxygen supply-demand relationship in the presence of a critical coronary stenosis.Acknowledgement I would like to appreciate for kindness of animal supply from the Laboratory Animal Center and extend my sincere appreciation to Pre-Prof. Yutaka Gotoh and Prof. Koji Sumikawa who kindly instructed and advised me. I would also like to extend my gratitude to Assistant Professor Fujigaki and Mr. Ureshino for technical assistance. A part of this study was reported at 37th Congress of the Japan Society of Anesthesiology, at Nagano, in May 11, 1990.References  1) Wang H, Liu L, Katz LR: A comparison of the cardiovascular effects    of sodium nitroprusside and trimethaphan. Anestesiology 46:40-48   (1977).  2) Tinker JH, Michenfelder JD: Sodium nitroprusside: Pharmacology,    toxicology and therapeutics. Anesthesiology 45:340-354 (1976).  3) Colley PS, Sivarajan M: Regional blood flow in dogs during halo-   thane anesthesia and controlled hypotension produced by nitro-   prusside or nitroglycerin. Anesth. Analg. 63:503-510 (1984).  4) Fukusaki M, Miyako M, Fukui S, et al: Hemodynamics during in-   duced hypotension with continuous administration of nicardipine.    Masui 35:551-556 (1986).  5) Lambert CR, Hill JA, Nichols WW, et al: Coronary and systemic   hemodynamic effects of nicardipine. Am. J. Cardiol. 55:652-656   (1985). 6) Takenaka T: Pharmacological studies of Ca"-antagonist: Evaluation    of cardiovascular, autonomic and smooth muscle effects of a new Ca"    -antagonistic vasodilator, 2, 6-dimethyl-4- (3-nitrophenyl) -1, 4-dihy-   dropyridine-3, 5-dicarboxylic acid 3-{2-(n-benzyl-n-methylamin o)}    ethyl ester 5-methyl ester hydrochloride (YC-93) and its mechanisms    of the action, J. Med. Soc. Toho, Japan 26:48-81 (1979). 7) Yamamura H, Inada Y, Fujita T, et al: The safety of prostaglandin E,    (G511) in induced hypotension during surgery in patients complicated    with ischemic heart disease. Masui 36:527-541 (1987).  8) Goto F, Otani E, Kato S, et al: ProstaglandinE, as a hypotensive drug    during general anaesthesia. Anaesthesia 37:530-535 (1982). 9) Fukusaki M, Konno K, Haseba S, et al: The effects of controlled    hypotension induced by prostaglandinE, and trimethaphan on coro-   nary and systemic hemodynamics and myocardial contractility. Masui   31:364-372 (1982). 10) Tamai J, Nanto S, Taniura K, et al: Acute effects of nicardipine    hydrochloride on hemodynamics, coronary circulation and myocardial    melabolism. Respiration and Circulation 35:549-552 (1987).11) Sha K, Miyata Y, Nagahara T, et al: Effects of controlled hypotension    induced by prostagladinE, on the cerebral blood flow. masui   39:138-143 (1990). 12) Yoda K, Hirose M, Sakai K, et al: Vasodilating therapy with prosta-   glandinE, in anesthetized patients with heart failure. Journal of Kyoto    Prefectural University of Medicine 98:631-637 (1989). 13) Yoshimine K, Oda T, Yoshimura N: Clinical application of prosta-   glandinE, for hypotensive anesthesia. Masui 30:664-671 (1981). 14) Elzinga WE, Skinner DB: Hemodynamic characteristics of critical    stenosis in canine coronary arteries. J. Thorac Cardiovasc Surg 69217   (1975). 15) Buffington CW: Hemodynamic determinants of ischemic myocardial    dysfunction in the presence of coronary stenosis in dogs. Anesthe-   siology 63:651-662 (1985). 16) Lowe JE, Cummings RG, Adams DH, et al: Evidence that ischemic    cell death begins in the subendocardium independent of variations in    collateral flow or wall tension. Circulation 68:190-202 (1983). 17) Weiss HR, Neubauer JA, Lipp JA, et al: Quantitative determination of    regional oxygen consumption in the dog heart. Circ. Res. 42:394-401  (1978). 18) Gould KL, Lipscomb K, Calvert C: Compensatory changes of the    distal coronary vascular bed during progressive coronary constriction.    Circulation 51:1085-1094 (1975). 19) Yasuoka M, Kokubo S, Okazaki K, et al: The effect of halothane on    ischemic myocardium. -2. Observation on regional blood flow distri-   bution. Masui 28:42-49 (1979). 20) Waters DD, Forrester JS: Myocardial ischemia: Detection and quanti-   tation. Ann. Inter. Med. 88:239-250 (1978). 21) Gertz EW, Wisneski JA, Neese R, et al: Myocardial lactate extraction:    Multi-determined metabolic function. Circulation 61:256-261 (1980). 22) Buffington CW: Impaired systolic thickening associated with halo-   thane in the presence of a coronary stenosis is mediated by changes in    hemodynamics. Anesthesiology 64:632-640 (1985).

https://nagasaki-u.repo.nii.ac.jp/?action=repository_action_common_download&item_id=22040&item_no=1&attribute_id=18&file_no=1

Effects of Nicardipine and Prostaglandin E1 on Coronary Hemodynamics in Dogs with Coronary Artery Stenosis.

Abstract

Similar works

Full text

Available Versions

Nagasaki university's Academic Output SITE

Nagasaki University's Academic Output SITE: NAOSITE