Studies on the Carotid Body and the Carotid Sinus Circulatory Effects Of
Total Page:16
File Type:pdf, Size:1020Kb
Studies on the Carotid Body and the Carotid Sinus Circulatory Effects of the Carotid Chemoreflex Takashi SASAKI, M.D. SUMMARY Previously, carotid chemoreflex and baroreflex have been reported, although for the most part of these mechanisms have not been clarified. In this experiments, circulatory effects of the carotid chemoreflex were investigated in the anesthetized dogs. Chemoreflex was performed with Lobeline (0.02mg, 1ml) and potassium cyanide (KCN, 1%, 1ml) through the catheter inserted to the carotid sinus. Continuously, during experi- ments, systolic blood pressure (S.P), diastolic blood pressure (D.P), systolic pulmonary blood pressure (SPaP), diastolic pulmonary blood pressure (DPaP), respiration and pulse rate were recorded simultaneously in the closed chest dogs. Cardiac output, pulmonary blood flow, coronary blood flow, S.P, D.P, SPaP, DPaP, and pulse rate were examined in the con- trolled breathing of the open chest dogs. In each experiment, during and after reflex, blood gas, HCO3-, and pH were measured. However, none of them were changed by these re- flexes. In the case of the closed chest dogs, chemoreflex by Lobeline did not change S.P and D.P, but SPaP was increased by 22.54%, significantly. DPaP was increased by 18.14%. Respiration rate was increased by 26.46% significantly. Heart rate was decreased by 9.15%. In the open chest dogs, chemoreflex by Lobeline increased S.P and D.P by 13.05% and 14.58% significantly . SPaP and DPaP were increased by 22.19% and 21.97% significantly . Pulmonary resistance was increased by 28.57% significantly . Pulmonary blood flow was decreased by 9.7% significantly. In the open chest dogs, chemoreflex with KCN increased S.P, D.P, and SPaP by 21.59%, 21.39%, and 41.02% significantly. Pulmonary resistance was increased by 20% significantly . Pulmonary blood flow was decreased by 10.43%. Cardiac output was not changed but coronary blood flow was increased by 6.50% significantly. It should be noted here that the carotid chemoreflex caused the hyperrespiration, the changes of pulmonary arterial blood pressure , pulmonary resistance, and pulmonary blood flow significantly, but these From the Second Department of Internal Medicine , Nihon University School of Medicine (De- partment of Cardiovasology, Surugadai Nihon University Hospital) , Tokyo.Thi s report was made according to the statement at th e 36th Annual Meeting of Japanese Cir- culation Society, April, 1972. Received for publication August 13, 1973. 539 Jap Heart J. 540 SASAKI November, 1973 hemodynamic changes are capable of being separated from the effects of hyperrespiration through the chemoreflex mechanism. Additional Indexing Words: Carotid chemoreflex Carotid chemoreceptor stimulation Sponta- neous breathing Controlled breathing Lobeline KCN EYMANS and Heymans demonstrated the presence of chemically sen- sitive nerve receptors in the region of the aortic arch in 1927.1) De Castro was the first to suggest that the carotid body subserved a chemosensory function.2) Briefly, it was shown that perfusion of the vascu- larly isolated, innervated, carotid body by blood of abnormal chemical com- position provoked reflex responses of respiration and blood pressure. Hypoxic hypoxia, hypercapnia or acidity of the perfusion fluid were found to cause reflex hyperpnea and hypertension which were abolished by section of the corresponding sinus nerve.3) As a series, studies on the carotid bodies and the sinus reflexes were started by this clinic 9 years ago.4)-9) Hemodynamic changes of the carotid chemoreceptor stimulation on cardiovascular systems are not yet clarified, and this time circulatory effects of the carotid chemoreceptor stimulation were investigated in the closed chest dogs and in the open chest dogs. METHODSAND MATERIALS Experiments were performed on 20 dogs weighing 10 to 15Kg, of either sex. Anesthesia was induced with sodium pentobarbital 0.5mg/Kg intravenously. The common carotid arteries were exposed and both right external and internal carotid arteries were also revealed. Catheter was inserted through the external carotid artery and positioned in the common carotid artery. Another catheter was in- serted from the external carotid vein, through the right atrium and the ventricle to the left pulmonary artery. Pulmonary arterial pressure and right ventricular pressure were recorded through the catheter. Systemic arterial pressure was re- corded through the catheter inserted to the femoral artery. Electro-cardiogram was also recorded. Lobeline (0.02mg), potassium cyanide (KCN, 1%) were infused into the sinus through the catheter. Closed chest experiments were performed by measuring systemic arterial blood pressure (S.P and D.P), pulmonary arterial blood pressure (SPaP and DPaP), respiration and pulse rate continuously before and after the infusion of drugs. Under controlled breathing by tracheal intubation, the chest was opened. The respirator was kept at the rate of 22 breaths/min, tidal volume was 200-250ml of air. Left lateral thoracotomy was performed in the fourth intercostal space. The heart was exposed and electromagnetic flow probes (Nihon Koden, MP-5 type) were placed around the thoracic aorta, left pulmonary artery and left circumflex Vol.14 CAROTID CHEMOREFLEX 541 No.6 Fig. 1. Schema for setting of the carotid chemoreflex, non-cannulating probes of cardiac output, pulmonary blood flow and coronary blood flow. Catheter for systemic blood pressure, pulmonary blood pressure and right ven- tricular pressure. coronary artery. Cardiac output, pulmonary blood flow and coronary blood flow were induced into the recorder by these probes. Systemic arterial pressure, right ventricular pressure and pulmonary blood pressure were measured through the catheter connected to the pressure transducers (Nihon Koden, MPF type). The isometric time tension index (dp/dt/IIT) was calculated by using the electro- cardiogram, right ventricular pressure and right ventricular dp/dt. Blood gases and pH were determined by the I.L meter (Instrumentation Laboratory Inc, model 113 and 127). Pulmonary vascular resistance was calculated as the quotient of the mean pulmonary arterial pressure (mmHg) and the mean pulmonary blood flow (ml/min), and was shown in mmHg/ml/min. Systemic vascular resistance was calculated from the mean aortic pressure (mmHg) and cardiac output (ml/min), and was shown in mmHg/ml/min. The standard II lead electrocardiogram was used for measurements of the heart rate. Just before the experiments, 1ml of normal saline was rapidly infused into the carotid sinus through the catheter, and it was confirmed that no changes took place. 542 SASAKI Jap. Heart J. November, 1973 Then, Lobeline and KCN were infused into the catheter . After 0.5-1.0sec from the onset of the pulmonary circulatory changes due to the carotid sinus infusion of drugs, systemic arterial pressure began to rise. The changes were shown at the time of maximal effects by the carotid chemo- receptor stimulation as determined by the highest point in aortic pressure, which occurred about 5-6sec after the onset of the carotid chemoreceptor stimulation. Results of each experiment were revealed by the percentage at the level of of the baseline values before the carotid chemoreceptor stimulation. Systemic blood pressure, pulmonary blood pressure, pulmonary blood flow, heart rate, cardiac output, coronary blood flow, right ventricular pressure and RVPdp/dt were recorded by the multiple channel recorder (Nihon Kohden, WI- 180) simultaneously. The data were statistically examined by Student's T-test. RESULTS Carotid chemoreceptorstimulation by Lobeline in the closed chest dogs The changes of the mean values, the standard deviation, and the statis- tical significance of changes are shown in Table I. Systolic blood pressure and diastolic blood pressure were changed not significantly. Systolic pulmonary blood pressure increased by the difference Table I. Effects of the Carotid Chemoreflex by Lobeline in the Closed Chest Dogs S.P: Systolic pressure (mmHg), D.P: Diastolic pressure (mmHg), S-PaP: Systolic pulmonary pressure (mmHg), D-PaP: Diastolic pulmonary pressure (mmHg), H.R: Heart rate (beats/min), Breathing: Breathing rate/min, R.V.P: Right ventricular pressure (mmHg), dp/dt/IIT: Isome- tricti me tension index, P.C: Percent change, P: P-value, P-values were calculated using Student's T-test, N: Number of experiments, n.s: not significant, S.D: Standard deviation, Lobeline: 0.02mg, 1ml. Vol.14 CAROTID CHEMOREFLEX 543 No.6 of 7.16•}4.67mmHg (percent change: 22.54%) from 31.76•}18.25mmHg, significantly. Diastolic pulmonary blood pressure increased (P.C: 18.14%), but not significantly. Heart rate decreased (P.C: 9.15%), but not significant- ly. Breathing rate increased by the difference of 2.69•}2.58 rate/min (P.C: 26.46%) from 10.17•}8.56 rate/min, significantly. Right ventricular pressure and isometric time tension index (dp/dt/IIT) were not changed. Carotid chemoreceptor stimulation by Lobeline in the open chest dogs The changes are shown in Table II. The control systolic blood pressure was 128.26•}27.38mmHg and con- trol diastolic blood pressure was 80.35•}4.02mmHg. After carotid chemo- receptor stimulation, systolic blood pressure increased by 16.74•}23.32mmHg (P.C: 13.05%) and diastolic blood pressure increased by 11.72•}11.54mmHg Table II. Effects of the Carotid Chemoreflex by Lobeline in the Open Chest Dogs S.P: Systolic pressure (mmHg), D.P: Diastolic pressure (mmHg), S-PaP: Systolic pulmonary pressure (mmHg), DPaP: Diastolic pulmonary pressure (mmHg), P.B.F: Pulmonary blood flow (ml/min), H.R: Heart rate (beats/min), C.O: Cardiac output (ml/min), C.B.F: Coronary blood flow (ml/min), P.R: Pulmonary vascular resistance (mmHg/ml/min), S.R: Systemic vascular resistance (mmHg/ml/min), R.V.P: Right ventricular pressure (mmHg), dp/dt/IIT: Isometric time tension index, P.C: percent changes, P: P-value, P-values were calculated using Student's T-test, N: Number of experiment, n.s: not significant, S.D: Standard deviation , Lobeline: 0.02mg, 1ml. Jap. Heart J. 544 SASAKI November, 1973 (P.C: 14.58%), significantly.