Myocardial blood flow regulation relative to left ventricle pressure and volume in anesthetized dogs

The influence of left ventricle pressure and volume changes on coronary blood flow was investigated in eight anesthetized dogs. Coronary artery pressure-flow relationships were determined at two levels of left ventricular pressure and volume. The distribution of blood flow within the myocardium was also determined when these relationships varied. Reducing left ventricle pressures and volumes increased heart rate. Rate-pressure product, diastolic coronary pressure, myocardial O2 consumption, total, subendocardial and subepicardial flow decreased. Hematocrit and blood gas data were unchanged. The pressure-flow relationships were shifted leftward (p = 0.001) but the range of autoregulation was not altered. At low left ventricle pressures and volumes, the lower coronary artery pressure limit was shifted leftward (from 75 to 45 mm Hg (1 mm Hg = 133.3 Pa)), while total, subendocardial, and subepicardial blood flow did not change compared with the control. Below the lower coronary artery pressure limit, subendocardial but not subepicardial flow decreased, resulting in maldistribution of flow across the left ventricular wall. When coronary pressure was reset between control and the lower coronary artery pressure limit, subendocardial flow was restored. These results show that the lower coronary artery pressure limit can be shifted leftward while the distribution of blood flow across the left ventricular wall is preserved.     

The effects of ethanol on pancreatic blood flow in awake and anesthetized dogs

The pathophysiology of alcohol-induced acute pancreatitis is not clear. Ischemic injury has been suggested as a possible mechanism. To examine the effects of ethanol on pancreatic and splanchnic blood flow, measurements were made in fasted, conditioned awake dogs before and after iv infusion of ethanol (1.7 g/kg). At 30 min blood ethanol concentration ranged between 60 and 150 mg/dl and at 60 min between 166 and 350 mg/dl. Although cardiac output, aortic pressure, left atrial pressure, and arterial pH did not change, pancreatic flow declined by 39 +/- 12 ml/min/100 g, P less than 0.05 (from 173 +/- 10 ml/min/100 g) at 30 min and was still depressed (by 27 +/- 12 ml/min/100 g, P less than 0.05) at 60 min. Concomitantly, hepatic arterial flow increased. While hepatic and pancreatic flow changed inversely, the correlation (r = -0.17) of these changes was not significant. At comparable blood ethanol concentrations in pentobarbital-anesthetized dogs hepatic arterial flow increased by 11 +/- 3 ml/min/100 g, P less than 0.01 (from 24 +/- 5 ml/min/100 g), but pancreatic flow did not change. Thus, in the awake dog at blood levels that would produce mild to moderate alcoholic intoxication in man, ethanol reduces pancreatic flow. Although hepatic flow increases concomitantly, the relationship of these changes appears to be independent.     

A technique for measurement of retrograde coronary blood flow in intact anesthetized dogs.

A technique for measurement of retrograde coronary blood flow in intact anesthetized dogs is described. Occlusion of the coronary artery is produced by the inflation of a small rubber balloon at the tip of a no. 9 cardiac catheter placed under fluorescopy in a branch of the left coronary artery. Blood which bleeds back from the occluded coronary artery through the no. 9 catheter is diverted into a small reservoir of 1-ml capacity. The time to fill this reservoir is recorded electrically. Retrograde coronary blood flow is calculated from the time required to fill this reservoir. Results indicate good repeatability of meadurements. The technique seems to be a simple, adequate, and convenient means for assessing agents for possible vasodilator action on the collateral circulation in intact animals.     

Compression induced by RV pressure overload decreases regional coronary blood flow in anesthetized dogs

Pulmonary artery constriction (PAC), a model of right ventricular (RV) pressure overload, flattens or inverts the septum and may flatten the left ventricular (LV) free wall. Finite element (FE) analysis predicts that such deformations may cause substantial compression. This study tests the hypothesis that deformation-induced myocardial compressive stress impedes coronary blood flow (CBF). Colored microspheres ( approximately 2 x 10(6)) were injected into the left atrium of 13 open-chest, anesthetized dogs under control conditions and during PAC, which decreased the end-diastolic transseptal pressure gradient (LV - RV) from 1.6 +/- 1.3 to -3.4 +/- 1.7 mmHg. Septal and LV deformation was assessed with the use of two-dimensional echocardiography, and by FE analysis, the hydrostatic component of stress was assessed. Postmortem, a 2.5-cm wide, LV equatorial ring was divided into 16 endocardial and epicardial samples. PAC decreased CBF in the FE-predicted compression zones, areas with the greatest compression having the greatest reductions in CBF. During PAC, compression reached a maximum of 25.3 +/- 1.8 mmHg on the (LV) endocardial sides of the RV insertion points, areas that saw CBF decrease from 1.05 +/- 0.08 to 0.68 +/- 0.05 ml.min(-1).g(-1) (P < 0.001), more than 30%. CBF decreased (from 1.08 +/- 0.07 to 0.81 +/- 0.07 ml.min(-1).g(-1); P < 0.001) on the RV side of the midseptum, an area with as much as 16.0 +/- 1.0 mmHg of compression. Overall, average compressions of 10 mmHg decreased CBF by approximately 30%. We conclude that acute RV pressure overload deforms the septum and LV and induces compressive stresses that reduce CBF substantially. This may help explain why some patients with pulmonary hypertension and no critical coronary disease have chest discomfort indistinguishable from angina pectoris.     

Myocardial tissue pressure and blood flow during coronary sinus pressure modulation in anesthetized dogs.

To determine whether coronary sinus outflow pressure (Pcs) or intramyocardial tissue pressure (IMP) is the effective back pressure in the different layers of the left ventricular (LV) myocardium, we increased Pcs in 14 open-chest dogs under maximal coronary artery vasodilation. Circumflex arterial (flowmeter), LV total, and subendocardial and subepicardial (15-microns radioactive spheres) pressure-flow relationships (PFR) and IMP (needle-tip pressure transducers) were recorded during graded constriction of the artery at two diastolic Pcs levels (7 +/- 3 vs. 23 +/- 4 mmHg). At high Pcs, LV, aortic and diastolic circumflex arterial pressure, heart rate, myocardial oxygen consumption, and lactate extraction were unchanged; IMP in the subendocardium did not change (130/19 mmHg), whereas IMP in the subepicardium increased by 17 mmHg during systole and 10 mmHg during diastole (P < or = 0.001), independently of circumflex arterial pressure. Increasing Pcs did not change the slope of the PFR; however, coronary pressure at zero flow increased in the subepicardium (P < or = 0.008), whereas in the subendocardium it remained unchanged at 24 +/- 3 mmHg. Thus Pcs can regulate IMP independently of circumflex arterial pressure and consequently influence myocardial perfusion, especially in the subepicardial tissue layer of the LV.     

Prostaglandin E1 increases blood flow to the cervix uteri

PGE₁ occurs in high concentration in seminal fluid and is apparently necessary for normal fertility, although its specific function(s) is not known. We investigated the possibility that PGE₁, at seminal fluid concentration, could increase cervical blood flow and, thus, potentially alter cervical mucus properties, including 0₂ concentration. Fifteen μg PGE₁/ml placed directly on the cervix uteri increased cervical blood flow in anesthetized dogs from 0.8±0.7 to 5.7±5.1 ml/gomin 5 min following application without affecting arterial pressure or hepatic or renal blood flow. Seminal PGE₁ may have effects upon oxygen tension in the cervical mucus, as well as aiding leukocyte accumulation in the cervical canal, by increasing cervical blood flow.     

Pulmonary blood flow distribution in anesthetized ponies.

Results of recent investigations in humans and dogs indicate that gravity-independent factors may be important in determining the distribution of pulmonary blood flow. To further evaluate the role of gravity-independent factors, pulmonary blood flow distribution was examined using 15-microns radionuclide-labeled microspheres in five prone ponies over 5 h of pentobarbital sodium anesthesia. The ponies were killed, and the lungs were excised and dried by air inflation (pressure 45 cmH2O). The dry lungs were cut into transverse slices 1-2 cm thick along the dorsal-ventral axis, parallel to gravity. Radioactivity of pieces cut from alternate slices was measured with a gamma well counter. The main finding was a preferential distribution of pulmonary blood flow to dorsal-caudal regions and higher flow in the center of each lung slice when compared with the slice periphery. Flow was lowest in cranial and ventral areas. Differences of +/- 2 SD were observed between core and peripheral blood flow. No medial-lateral differences were found. Pulmonary blood flow distribution did not change over 5 h of anesthesia, and the basic flow pattern was not different in the left vs. right lung. These results suggest that in the intact prone mechanically ventilated pony (inspired O2 fraction greater than or equal to 0.95) factors other than gravity are primary determinants of pulmonary blood flow.     

A microsphere study on the effects of somatostatin and secretin on regional blood flow in anesthetized dogs

The endogenous peptides somatostatin and secretin are effective in the therapy of upper gastrointestinal tract bleeding and acute pancreatitis. The clinical effects may be partly brought about by changes in the regional blood flow. To evaluate the effects of somatostatin (50 and 100 μg/min over 6–8 min) and secretin (0.1 and 0.5 U · kg^?1 · min^?1 over 3–5 min) on tissue blood flow, particularly of the gastrointestinal tract, the tracer microsphere reference sample method was used in anesthetized dogs.Infusion of somatostatin significantly diminished gastric and pancreatic blood flow whereas no changes of duodenal and ileal blood flow could be obtained. Blood flow through spleen, kidneys and adrenal glands was increased but no changes were observed in the blood flow of other tissues. Cardiac hemodynamics remained unchanged.Secretin increased the blood flow of the duodenum, the kidneys and the adrenal glands and diminished gastric blood flow without changing pancreatic, ileal, hepatic, pulmonary and muscle blood flow. Cerebral, pituitary and myocardial blood flow was increased by a higher dose of secretin. It also evoked a slight but significant positive ino- and chronotropic effect. Since secretin and somatostatin differ in their respective effects on gastrointestinal blood flow it is suggested that the previously reported beneficial effects of both peptides on upper gastrointestinal bleeding cannot solely be attributed to changes in regional blood flow.     

Ventilatory responses to intravenous and airway CO2 administration in anesthetized dogs

The ventilatory responses to steady-state venous CO2 loading (iv CO2) and CO2 inhalation have been observed in chloralose-urethan-anesthetized dogs. Intravenous CO2 was administered by increasing the CO2 fraction of gas ventilating a membrane gas exchanger in an arteriovenous bypass; blood flow rate was fixed at 30 ml/min. During the study, we identified a time-dependent hyperventilation in all 14 experimentally treated dogs and in 4 additional sham-treated dogs. When we tested 8 of these animals with a protocol having small progressive increments in iv CO2 loading rate, we observed a response approaching isocapnia during iv CO2 and a large hypocapnia when we returned to control conditions. The use of a randomized protocol in 6 animals demonstrated the necessity of accounting for this systematic base-line shift, because before doing so the response depended more on the passage of time than on the nature of the CO2 load. After this analytical adjustment was made, there was no significant difference between the respiratory controller gains (delta nu E/delta Paco2) for inhaled and iv CO2.     

Tachyphylaxis to inhaled aerosolized histamine in anesthetized dogs

Three consecutive dose-response curves to inhaled aerosolized histamine, separated by 1-h intervals, were obtained in 20 anesthetized mongrel dogs. In general, successive histamine dose-response curves shifted progressively rightward. Changes in pulmonary resistance (RL) and dynamic compliance (Cdyn) in response to low concentrations of histamine were reproducible, but responses to high concentrations (sufficient to at least double RL or decrease Cdyn by at least 30%) decreased on successive dose-response curves. The concentration of histamine required to double RL increased significantly (P less than 0.05) from 1.01 mg/ml on the first to 1.62 and 2.02 mg/ml on the second and third dose-response curves. In contrast, consecutive methacholine dose-response curves were not significantly different. Indomethacin pretreatment (5 mg/kg iv) prevented histamine tachyphylaxis, whereas atropine (4 mg iv) did not. However, indomethacin did not alter base-line pulmonary mechanics or histamine responsiveness as measured on the first dose-response curve. We conclude that tachyphylaxis to inhaled aerosolized histamine occurs in anesthetized dogs. Our results are consistent with an important role for endogenous prostaglandins in modulating the airway responses to repeated histamine exposures.     

Respiratory response to partial paralysis in anesthetized dogs

The ability to maintain alveolar ventilation is compromised by respiratory muscle weakness. To examine the independent role of reflexly mediated neural mechanisms to decreases in the strength of contraction of respiratory muscles, we studied the effects of partial paralysis on the level and pattern of phrenic motor activity in 22 anesthetized spontaneously breathing dogs. Graded weakness induced with succinylcholine decreased tidal volume and prolonged both inspiratory and expiratory time causing hypoventilation and hypercapnia. Phrenic peak activity as well as the rate of rise of the integrated phrenic neurogram increased. However, when studied under isocapnic conditions, increases in the severity of paralysis, as assessed from the ratio of peak diaphragm electromyogram to peak phrenic activity, produced progressive increases in inspiratory time and phrenic peak activity but did not affect its rate of rise. After vagotomy, partial paralysis induced in 11 dogs with succinylcholine also prolonged the inspiratory burst of phrenic activity, indicating that vagal reflexes were not solely responsible for the alterations in respiratory timing. Muscle paresis was also induced with gallamine or dantrolene, causing similar responses of phrenic activity and respiratory timing. Thus, at constant levels of arterial CO2 in anesthetized dogs, respiratory muscle partial paralysis results in a decrease in breathing rate without changing the rate of rise of respiratory motor activity. This is not dependent solely on vagally mediated reflexes and occurs regardless of the pharmacological agent used. These observations in the anesthetized state are qualitatively different from the response to respiratory muscle paralysis or weakness observed in awake subjects.(ABSTRACT TRUNCATED AT 250 WORDS)     

Prostaglandin I2 (prostacyclin).

Prostaglandin I2 (PGI2), or prostacyclin, is a recently discovered prostaglandin that affects many organ systems. It is both a potent inhibitor of platelet aggregation and a powerful vasodilator. The recent demonstration that it is the main prostaglandin synthesized by the blood vessel wall suggests that it may play an important role in limiting platelet-mediated thrombosis. However, despite considerable investigation, the exact physiological role of PGI2 has yet to be elucidated.     

Autoregulation of diaphragmatic blood flow in dogs

In eight anesthetized spontaneously breathing dogs, we determined whether diaphragmatic blood flow is dependent on arterial blood pressure (Pa) or whether it is autoregulated. We also determined whether diaphragmatic muscular activity affects the degree of autoregulation. We measured blood flow through the left phrenic artery (Qphr) with an electromagnetic flow probe and decreased Pa in steps by controlled hemorrhage. Phrenic venous blood was sampled to allow the calculation of diaphragmatic O2 consumption (VO2phr). Diaphragmatic energy demands were varied by using three inspiratory resistances (R1, R2, and R3), which increased peak transdiaphragmatic pressure two-, three-, and fourfold, respectively. During quiet breathing, Qphr was independent of Pa between Pa of 90 and 120 mmHg (i.e., plateau of pressure-flow relation), but at lower Pa, Qphr was directly related to Pa. During inspiratory loading, the Qphr plateau ended at a higher Pa than with quiet breathing, but within the normal ranges of Pa there still was a plateau. VO2phr at a given work load was constant between Pa of 70 and 120 mmHg, but at Pa of 50-55 mmHg, VO2phr declined with all work loads. We conclude that in spontaneously breathing dogs 1) Qphr is autoregulated over the normal range of blood pressures and 2) VO2phr is maintained over wider ranges of Pa than Qphr.