Physiol. Res. 43: 373-381, 1993 Diastolic-systolic Differences in Coronary Blood Flow: Effect of Stenosis and Tachycardia in the Anaesthetized Dog D. GATTULLO, M. DAMBROSIO, A. FEDERICI, R.J. LINDEN1, G. LOSANO, P. PAGLIARO Department of Anatomy and Human Physiology, University of Torino, Italy and 1 Division of Biomedical Science, King's College, London, UK Received April 13, 1993 Accepted August 2, 1993 Summary Blood flow in the left coronary artery is lower in the systole than in the diastole. This difference is attenuated in the presence of severe stenosis, which affects the flow more during the diastole than during the systole. Some explanations have been suggested: epicardial vasodilatation distal to the stenosis, a decrease in myocardial contractility and impairment of the intramyocardial pump effect. The present investigation in anaesthetized dogs showed that, in the presence of severe stenosis, the attenuation of the diastolic-systolic coronary flow differences occurs together with distal vasodilatation in the epicardial layers of the myocardium. This attenuation may be even greater if further vasodilatation is induced by increasing the heart rate. Mo evidence of reduced myocardial contractility was observed. In addition, it was found that the onset of the systolic rise of the coronary blood pressure below the stenosis occurs before that of the aortic blood pressure. This finding may serves as evidence for the role played by the intramyocardial pump mechanism in causing the systolic reduction of coronary flow. Since this mechanism is believed to propel some blood back into the aorta during the systole, the impairment of this retrograde flow caused by the stenosis could also account for the reduction of the diastolic-systolic flow differences. Key words Coronary flow - Coronary stenosis - Intramyocardial pump Introduction Arterial blood flow shows rhythmic Spaan et al. 1986, Spaan and Dankelman 1989). The fluctuations depending on cardiac activity, i.e. an extent of the systolic reduction of coronary flow has increase during the systole and a decrease during the recently been attributed to the myocardial contractility diastole. This general pattern is reversed in large (Krams et al. 1989b). It is known that the severe coronary arteries, where the flow in the systole is lower stenosis of a large coronary epicardial artery not only than in the diastole, because myocardial contraction causes a reduction in the mean flow, but also modifies compresses the intramyocardial vessels (Gregg and the pattern of the phasic flow (Furuse et al. 1975, Green 1940, Wiggers 1954, Gregg et al. 1965, Klocke Mates et al. 1978). There is a decrease in diastolic 1976). The waterfall model of Permutt and Riley coronary flow which is not accompanied by a similar (1963) has been used to describe the systolic reduction decrease in systolic coronary flow, the latter being less of coronary flow (Downey and Kirk 1975). Another reduced, unchanged or slightly increased, so that the model of the coronary circulation, "the intramyocardial differences of diastolic-systolic flow are attenuated. pump model" suggested by Spaan and his group The hypotheses proposed to explain the above provides a quantitative relationship between the changes have considered that myocardial contractility is myocardial systolic compression and diastolic reduced, that vasodilatation occurs in the epicardial relaxation and the diastolic-systolic coronary flow layers of the myocardium distal to the stenosis (Mates differences (Spaan et al. 1981, Bruinsma et al. 1985, etal. 1978) and that the effect of the intramyocardial 374 Gattullo et al. V o l. 42 pump is impaired (Spaan et al. 1981). In the present in a dose of 30 mg/kg. After the trachea had been study we tried to verify the hypothesis that intubated with a Magill tube, artificial positive pressure vasodilatation is a major factor in the attenuation of ventilation was started using a Harvard respiratory the diastolic-systolic coronary flow differences in the pump (Model 607, Harvard Apparatus Co., Dover MA, presence of severe stenosis. We examined the diastolic- U.SA.). systolic coronary flow differences before and after the The neck was opened along the ventral production of severe flow limiting stenosis; then, with midline and the right external jugular vein, the the stenosis in place, the heart rate was increased to common carotid arteries and the vagal nerves were raise oxygen consumption resulting in vasodilatation. dissected free. A catheter was inserted into the vein to Records of the left ventricular pressure were used to administer the solutions needed for the maintenance of assess possible changes in myocardial contractility. anaesthesia and of the acid-base balance. Two Preliminary results of this study have been catheters connected to Statham P23Db presented to the British Physiological Society (Gattullo electromanometers (Statham Laboratories, Hato Rey, et al. 1993). Puerto Rico) were inserted into the common carotid arteries: the tip of one was pushed into the aortic root Methods to transmit aortic blood pressure (ABP) near the coronary ostia; the tip of the other was pushed into the The experiments were performed on six left ventricle to transmit left ventricular pressure mongrel dogs weighing 18-27 kg. General anaesthesia (LVP). was induced by i.v. injection of sodium pentobarbitone F»g-1 Schematic drawing of the constrictor device. A= Micromanipulator. B= Joining support between the piston of the micromanipulator and the camera shutter release. C= Camera shutter release. D= Magnification of the perspex housing with the metal cylinder compressing the artery. The artery (a) is partially constricted by the metal cylinder (me). E= Positions on the heart of the constrictor, the flow probe (f), and the coronary pressure catheter (p). 1993 Coronary Stenosis in the Dog 375 After a left thoracotomy in the fourth Anaesthesia was maintained by continuous i.v. intercostal space, the pericardium was opened parallel infusion (12.5 /¿g/kg/min) of sodium pentothal, and an to the left phrenic nerve and the heart suspended in a hourly injection ( 1.0 /¿g/kg) of fentanyl (opiate-related pericardial cradle. To record coronary blood flow analgesic, Fentanest, Carlo Erba, Milano, Italy). (CBF), a flow probe connected to a 400 c.p.s. Samples of arterial blood were taken from the right electromagnetic flowmeter BL 310 (Biotronics femoral artery and analyzed for Po2, PCo2, pH, Laboratories Inc., Silver Spring, MD, U.SA.) was bicarbonate concentration and base excess using an placed around the initial part of the left circumflex IL 1302 gas analyzer (Instrument Laboratory System). coronary artery. Distal to the flow probe, a constrictor Acid-base and respiratory status were maintained device was placed around the artery (Dalla Valle and within normal limits of the dog (Altman and Dittmer Di Lavore 1988). The device surrounded the artery 1964) by regulating the respiratory pump and infusing, with curved housing of rigid Perspex and a metal a bicarbonate solution, when required. Body cylinder (Fig. 1) attached to a micromanipulator by a temperature was monitored by an Ellab DU rectal camera shutter release, about 20 cm long. The thermistor probe (Ellab Co., Copenhagen, Denmark) micromanipulator produced small movements in the and kept within normal limits using an electric pad metal cylinder which, when driven towards the housing, and/or an infrared ray lamp. constricted the artery to the required extent. Due to ECG, ABP, LVP, CBP, CBF, AF and the time the characteristics of the constrictor an eccentric rather trace were recorded using a DR -8 cathode ray recorder than a concentric stenosis could be obtained. The (Electronics for Medicine, White Plains, NY, U.SA.). extent of the constriction was read on the scale of the At the end of the experiments the animals micromanipulator. It was expressed in terms of were killed by i.v. injection of an excess of sodium percentage constriction, 100 % being the fully occluded pentobarbitone. artery and 0 % as the fully open vessel (Dalla Valle and Di Lavore 1988). The constrictor was also used to Experimental protocol occlude the artery for obtaining the level of the zero Following surgery, the experiments were flow line. started after a steady-state had been obtained with Another flow probe connected to a 1000 c.p.s. respect to the anaesthesia and the acid-base status. In 310 BL electromagnetic flowmeter was placed around each animal the heart was paced at the rate of 100 the ascending aorta, just beyond the aortic valve, to b.p.m. during the control period. Then the left record aortic flow (AF) assisting in the continuous circumflex coronary artery was constricted by about monitoring of the condition of the animal. 85 % of the range determined on the scale of the Coronary blood pressure (CBP) distal to the micromanipulator. Owing to the characteristics of the constriction was transduced by a third Statham P23Db arterial wall and the shape of the constrictor, it is electromanometer, connected to a catheter inserted possible only to indicate the degree of constriction in into the marginal artery, a branch of the left circumflex terms of a percentage change in the constrictor and not coronary artery. in terms of the actual reduction of the arterial lumen. After the vagi had been sutured, the right However, in order to quantitate the influence of the vagus distal to the occlusion was placed inside stenosis, the extent of changes in coronary resistance electrodes connected to a San’ei ES-103 stimulator has been assessed by calculating these changes in terms (San’ei Instruments Ltd.). Stimuli of 4 -7 V and 2 ms of the total coronary resistance (see below). With the in duration at 6 -8 c.p.s. were delivered to slow the artery constricted, the pacing was continued initially at heart rate and to enable pacing of the heart rate at 100 100 b.p.m. and then increased to 160 b.p.m.