Partial Aortic Occlusion Research Articles

Activation of heat-shock transcription factor by graded reductions in renal ATP, in vivo, in the rat.

Renal ischemia results in both a profound fall in cellular ATP and a rapid induction of the 70 kD heat-shock protein family, HSP-70. The present studies examined the relationship between cellular ATP and induction of the stress response in renal cortex. Cellular ATP, continuously monitored by in vivo 31P-NMR spectroscopy, was reduced and maintained at specific, stable levels in renal cortex by partial aortic occlusion for 45 min. Activation of heat-shock transcription factor (HSF) was detected by gel retardation assay and transcription was confirmed by Northern analysis. Activation of HSF was not present, and HSP-70 mRNA induction did not occur when ATP levels were maintained above 60% preocclusion (control) levels. Reduction in cortical ATP levels to 35-50% preocclusion values resulted in HSF activation and low-level expression of inducible HSP-70 mRNA. Cellular ATP of 20-25% control values resulted in a greater level of HSF activation and subsequent HSP-70 mRNA elaboration. HSF was activated at the end of 15 min of total occlusion. The studies indicate that a 50% reduction in cellular ATP in the renal cortex must occur before the stress response is detectable, that reduction of ATP below 25% control levels produces a more vigorous response, and that reperfusion is not required for initiation of a heat-shock response in the kidney. Cellular ATP, or the metabolic consequences associated with ATP depletion, may be a threshold factor for initiation of a stress response in the kidney.

Nonlinearity of the left ventricular end-systolic wall stress-velocity of fiber shortening relation in young pigs: A potential pitfall in its use as a single-beat index of contractility

Objectives. We sought to evaluate in the young heart the primary assumptions on which the current use of the mean “velocity of fiber shortening corrected for heart rate” as a noninvasive index of contractility are based.Background. End-systolic wall stress-velocity of fiber shortening relation has been applied as a single-beat, load-independent index of contractility in children. This use is based on poorly validated assumptions of linearity, parallel shifts with changing contractile state and inotropic sensitivity of the end-systolic wall stress-velocity of fiber shortening relation.Methods. In eight anesthetized young piglets, 5F micromanometric catheters were placed in the ascending aorta and balloon occlusion catheters in the descending aorta. End-systolic wall stress and velocity of fiber shortening were calculated from aortic pressure and M-mode echocardiography under six conditions: in three contractile states 1) baseline, 2) increased contractility during dobutamine infusion (10 μg/kg per min), and 3) decreased contractility after propranolol injection (1 mg/kg), each at two afterload states (normal and increased load by partial aortic occlusion).Results. Dobutamine increased and propranolol decreased afterloadd-matched velocity of fiber shortening corrected for heart rate significantly to 140% aid 77% of baseline, respectively. However, the slope of end-systolic wall stress-velocity of fiber shortening was (251% of baseline) during dobutamine infusion, which also significantly decreased wall stress, and was much less (27% of baseline) after propranolol injection, which increased wall stress.Conclusions. The velocity of fiber shortening corrected for heart rate did change predictably with changes in contractility and as such can be ued noninvasively in the temporal evaluation of individual patients undergoing therapeutic interventions or to define the natural history of a disease process. However, the relation on which it is based is not defined by parallel straight lines across contractile states, so that abnormal single measurements may reflect only the nonlinearity of the relation rather than in contractility. Thus, we recommend that the end-systolic wall stress-velocity of fiber shortening relation should not be used as a single-beat index of contractility.

PLASMA RENIN ACTIVITY DURING HYPOTENSIVE RESPONSES TO ELECTRICAL STIMULATION OF CAROTID SINUS NERVES IN CONSCIOUS DOGS

1. The interaction of electrical stimulation of the carotid sinus nerves (carotid sinus nerve stimulation, CSNS) with mechanisms of renin release was studied in conscious and unrestrained resting beagle dogs receiving a standardized diet (sodium intake, 4.5 mmol/kg bodyweight (bw); water intake, 91 mL/kg bw). 2. By CSNS, mean arterial blood pressure (MAP) was lowered for periods of 20 min to levels between 101 +/- 4 and 56 +/- 5 mmHg. 3. In another group of conscious dogs, renal perfusion pressure (RPP) was lowered to 95 +/- 4 mmHg for periods of 20 min by partial suprarenal aortic occlusion in order to assess the influence of a reduced RPP on plasma renin activity (PRA) without concomitant CSNS. 4. During CSNS, PRA increased markedly (> 100%) only when MAP was reduced below 75 mmHg. 5. With aortic constriction and an RPP of 95 mmHg, the increase in PRA was 955%, which is more than three-fold higher than the increase in PRA during CSNS at MAP levels < 65 mmHg (314%). 6. The observed responses indirectly support the hypothesis that basal activity in efferent renal nerve discharge is present even at rest and can be inhibited by CSNS, and furthermore suggests that CSNS attenuated the pressure-dependent renin release.

Left ventricular ejection activation in the in situ heart

We tested, in the in situ heart, the hypothesis that the end-systolic pressure (ESP) of small ejecting contraction (EC) is greater than that of an isovolumic contraction (IC) with a similar end-systolic volume. We produced ECs with varying amounts of ejection by partial aortic occlusion while measuring left ventricular pressure, one or two left ventricular dimensions (anteroposterior and septal-lateral), and aortic flow. In 11 dogs, we plotted ventricular pressure against the time integral of aortic flow of ECs and IC with the same end-diastolic anteroposterior dimension. The end-systolic pressure-volume line was drawn from the peak isovolumic pressure-volume point tangential to the left upper corner of the pressure-volume loop of ECs. The slope of the tangential line of the middle EC, whose stroke volume was 51 +/- 8% of that of the control EC, was decreased by 54 +/- 16% compared with that of the control EC. In eight dogs with two pairs of crystals, left ventricular volume was controlled by partial vena caval occlusion, and ICs were produced by total aortic occlusion. The end-systolic pressure of small ejections exceeded (11.3 +/- 7.7 mmHg, P less than 0.01) those of isovolumic contractions with the same end-systolic cross-sectional area, whereas the end-systolic pressure of beats with large ejections was similar (-9.4 +/- 14.4 mmHg, P = NS) to an IC with the same end-systolic cross-sectional area. We conclude that the end-systolic pressure-volume point of beats with a small ejection is located above the isovolumic end-systolic pressure-volume relation in the in situ dog left ventricle.

Regulation of plasma ANF after increases in afterload in conscious dogs

Although atrial stretch is the primary stimulus for atrial natriuretic factor (ANF) secretion, hormones may directly affect ANF secretion or may indirectly influence ANF by changing left ventricular afterload, thereby altering atrial stretch. To determine whether direct effects are important for the release of ANF in vivo, we measured changes in plasma ANF and in atrial wall function in the conscious dog after the administration of vasopressin, angiotensin II, and phenylephrine and by mechanically increasing left ventricular afterload by partial aortic occlusion. Injections of phenylephrine, angiotensin II, and arginine vasopressin (AVP) that were chosen to cause similar changes in systemic arterial pressure resulted in similar changes in atrial pressure and diameter. Maximum V wave atrial wall stress increased to 283 +/- 12, 311 +/- 41, 327 +/- 24, and 277 +/- 22 g/cm2 for AVP, angiotensin, phenylephrine, and occlusion, respectively, and plasma ANF increased to 242 +/- 81, 248 +/- 62, 299 +/- 95, and 190 +/- 53 pg/ml. There were significant linear correlations between left ventricular afterload and left atrial pressure, and each method for increasing left ventricular afterload shifted the position to the left on an atrial pressure-diameter, compliance curve, by a similar degree. Thus changes in left ventricular afterload result in changes in atrial wall function and similar changes in plasma ANF. No hormonal-specific increase in plasma ANF was found in conscious dogs after increases in afterload.

Volatile Anesthetic Effects on Left Ventricular Relaxation in Swine

The effects of halothane (0.5, 1.0, and 1.5%; n = 10), enflurane (1.0, 2.0, and 3.0%; n = 8), and isoflurane (0.75, 1.5, and 2.25%; n = 8) on isovolumic relaxation were studied in open-chest swine. The time constant for isovolumic left ventricular pressure decline, T, was determined at each anesthetic concentration at the intrinsic heart rate and during atrial pacing to 150 beats per min. The effect of increased left ventricular afterload on T was investigated by partial occlusion of the thoracic aorta to raise the left ventricular systolic pressure to baseline in the presence of volatile anesthetics, and 20% above baseline in the absence of volatile anesthetics. Heart rate and left ventricular systolic pressure decreased substantially with all three anesthetics, whereas left ventricular end-diastolic pressure increased (by 3-4 mmHg). Relaxation time constants increased with all three anesthetics at the intrinsic heart rate; when the heart rate was controlled by pacing, T increased in the halothane and enflurane, but not in the isoflurane, experiments. T was significantly prolonged (by 30-100%) by partial aortic occlusion in the presence of anesthetic, but not in the control measurements. T did not change significantly in the isoflurane experiments when atrial pacing was employed with partial aortic occlusion. The volatile anesthetics, particularly halothane, seem to impair the relaxation process of the left ventricle; further investigation of the mechanisms of this interference, such as anesthetic effects on intracellular calcium movement and total left ventricular load, is warranted.

Late-systolic pumping properties of the left ventricle. Deviation from elastance-resistance behavior.

Elastance-resistance [E(t)-R] representations of the left ventricle (LV) were evaluated for their ability to reproduce instantaneous pressure [P(t)] and outflow [Q(t)]. Experiments were performed in open-chest rats. P(t) and Q(t) were measured during steady-state ejecting beats and during a beat in which the aorta was suddenly clamped. The degree of clamping varied from partial to total occlusion. The total occlusion beat was considered an isovolumic beat that generated an isovolumic pressure [Piso(t)] with a characteristic time to maximal Piso(t) [Tpisomax]. In ejecting beats, 34% of stroke volume was delivered after Tpisomax. P(t) and Q(t) from the steady-state ejecting beats and Piso(t) from the clamped beat were then used to estimate parameters of an E(t)-R model. Components of P(t) and Q(t) not accounted for by E(t)-R were identified and termed extra-pressure [Pext(t)] and extra-outflow [Qext(t)]. Pext(t) and Qext(t) were near-zero valued until Tpisomax; then they became systematically positive and finally negative valued after end ejection. During partial aortic occlusion, P(t) was elevated and Q(t) was reduced. However, the time of ejection was extended, and the fraction of stroke volume delivered after Tpisomax increased as P(t) was made higher. Partial occlusion also prolonged the positive phase of Pext(t) and Qext(t). Elements possessing "active" and "deactive" properties were added to the E(t)-R model in an attempt to account for Pext(t) and Qext(t) during partial occlusion. Optional forms of these elements were considered. These expanded E(t)-R models were fitted to basal ejecting data and then asked to predict data from a partial occlusion beat. All expanded models failed to adequately predict the partial occlusion pressure and/or outflow. It was concluded that 1) late ejection was quantitatively important to LV pumping, 2) behavior during late ejection was inconsistent with E(t)-R, and 3) ad hoc modification of E(t)-R models was not likely to yield LV pumping models that could satisfactorily reproduce instantaneous P(t) and Q(t) behavior over the entire ejection period.

Effects of left ventricular loading by negative intrathoracic pressure in dogs.

There are many factors, both intrinsic and extrinsic to the left ventricle, that can affect its function when negative intrathoracic pressure is imposed. In this study, we examined whether the left ventricular response to the afterload imposed by negative intrathoracic pressure was similar to that imposed by partial aortic constriction. We used steady-state right heart bypass to control pulmonary venous return to the left ventricle and reflex blockade to maintain constant heart rate and contractility. To impose negative intrathoracic pressure we used a pressure chamber fitted over a midsternal thoracotomy, which allowed steady negative pressure to be applied to all intrathoracic surfaces. Left ventricular volumes were measured from biplane cineradiograms of multiple 1-mm markers implanted in the left ventricular midwall. With cardiac output and heart rate constant, we compared the left ventricular response to two different levels of negative intrathoracic pressure and to increasing aortic pressure by partial aortic constriction. In each case, negative intrathoracic pressure produced a rise in the left ventricular end-systolic and end-diastolic volumes as well as transmural pressures similar to the effects of partial aortic occlusion. Thus, when cardiac output, heart rate, and contractility are maintained constant and all external restraints on the left ventricle are removed, the left ventricle responds in a similar manner to an increase in hydraulic load whether produced by a decrease in intrathoracic pressure or by partial aortic occlusion.

Regional end-systolic pressure-length relationships using a volume-loading technique in the intact pig heart.

The purpose of this study was to characterize left ventricular systolic elastances as derived from pressure-segment length and pressure-diameter relationships, and to compare the resulting regional and global elastances to known changes in inotropy. Left ventricular pressure-segment length and pressure-diameter were varied in a series of consecutive beats by means of a volume-loading technique, and both regional and global relationships at 20-msec intervals throughout systole were found to be nonlinear and to exhibit hysteresis. In eight animals, regional hysteresis was present after vagotomy, propranolol (1.0 mg/kg), and atropine (0.1 mg/kg), and was present no matter whether hearts were loaded by volume (45-60 ml/sec) or by pressure (partial aortic occlusion) over a similar range of left ventricular systolic pressures. Elastance was linearly approximated by the slope of the major axis of the hysteresis loops. In each instance, elastance increased to a maximum and then decreased, thus defining end-systole. In seven animals, maximum elastance-length and -diameter were compared before and after treatments with dobutamine (5-13 micrograms/kg per min) and propranolol (6-51 micrograms/kg per min), or after induction of global ischemia. Dobutamine increased maximum elastance-diameter by 37% (P less than 0.01) and maximum elastance-length by 159% (P less than 0.05). Propranolol decreased maximum elastance-diameter by 27% (P less than 0.05) and maximum elastance-length by 6% (P = NS). Global ischemia (50% reduction in coronary flow) did not significantly change either maximum elastance-diameter or -length. However, with ischemia, the diameter intercept of maximum elastance-diameter increased by 24% (P less than 0.025), and the time to maximum elastance-length decreased by 33% (P less than 0.01). Comparing all interventions, the percent changes in maximum elastance-length and -diameter related directly but with a low correlation coefficient (r = 0.49). These differences in regional and global elastance suggest a complex relationship between regional and global myocardial mechanics, and may not necessarily reflect specific changes in contractility.

Increased sodium appetite and polydipsia induced by partial aortic occlusion in the rat.

Partly occluding the abdominal aorta between the renal arteries caused the rat to drink steadily increasing amounts of 2.7% NaCl when this solution and water were available. The increase in NaCl intake preceded the increase in water intake that also occurred after aortic occlusion, and intakes of both fluids were reaching maximal values 1-2 weeks after operation. The amounts of fluid drunk during the day increased greatly. This change in the pattern of drinking, together with the rise in fluid intake and the drop in food intake meant that drinking was less associated with feeding than it is in the normal rat. The rats went into fluid and electrolyte deficit within 24 h of partial aortic occlusion and remained in deficit for about a week (the duration of the balance experiment) despite increasing intakes of NaCl and water. Renal function was unimpaired during the first 2 weeks, and the abnormal signs were mainly and rapidly reversed by removal of the ischaemic kidney or administration of the angiotensin converting enzyme inhibitor, captopril. Therefore polydipsia and increased sodium appetite in the first 2 weeks after aortic occlusion were likely to have been caused by fluid deficit, with increased renin secretion from the ischaemic kidney contributing to both behaviours. Arterial blood pressure rose immediately after aortic occlusion, before the onset of increased drinking. Up to 3 weeks after operation the incidence and severity of the hypertension did not appear to depend on the spontaneous changes in intake of water or hypertonic NaCl.

Canine coronary venous pressures: responses to positive inotropism and vasodilation.

The epicardial coronary venous pressure in 16 dogs was compared with coronary arterial pressure as well as aortic, intraventricular, and intramyocardial pressures. Partial aortic occlusion augmented intraventricular (IVP), intramyocardial (IMP), aortic (AP), and coronary arterial pressures. Peripheral coronary venous pressure was also elevated. Dobutamine significantly augmented IVP and IMP but not aortic or central coronary artery pressures; this agent significantly elevated coronary venous systolic pressure (28/8 to 84/12 mmHg) (1 mmHg = 133.322 Pa). Nitroglycerine decreased IVP, IMP, and AP significantly. Central coronary arterial pressure also fell significantly, but coronary venous pressures remained unchanged. In contrast dipyridamole resulted in no change in IVP, IMP, AP, or coronary arterial systolic pressures; however, the peripheral coronary venous systolic pressure became significantly elevated. Thus the two vasodilators, nitroglycerine and dipyridamole, had different effects upon coronary venous pressure. These data reinforce the recently expressed view that coronary veins behave in a complex fashion and further suggest that their pressures are dependent upon coronary artery pressure, intramyocardial pressure, and coronary venous tone.

Pregnancy associated with partial aortic occlusion

in dense clumps adherent to the inner coat of the nuclear envelope toward the periphery. The age of the patient and the presence of vaginal bleeding caused by a nodular, ulcerated mass are consistent with a primary malignant melanoma of the vagina. As often seen with vaginal melanomas, the aggressive tumor led to the patient’s rapid death. With electron microscopy, it was possible to distinguish between those diagnoses which had been considered with the use of light microscopy. The diagnosis of a poorly differentiated squamous cell carcinoma was excluded by the lack of desmosomes and keratin; an extra-adrenal pheochromocytoma was eliminated by the lack of eccentrically placed, dense-core norepinephrine granules, and rhabdomyosarcoma was excluded by the absence of rhabdomyoblasts and filaments similar to skeletal muscle fibers.2 The features of this tumor characteristic of an amelanotic malignant melanoma were the presence of junctional activity in the vaginal epithelium and the presence of numerous premelanosomes in the cytoplasm. The diagnoses which had been considered included a benign tumor, carcinoma, or sarcoma. The importance of electron microscopy in distinguishing between the possible diagnoses relates to the different prognostic and therapeutic factors in all these lesions. It is recommended, therefore, that when the diagnosis of a pelvic tumor is unclear by light microscopy, the electron microscope should be used to aid in making the correct diagnosis.

The influence of left ventricular volume and wall motion in myocardial images.

We studied 10 dogs to determine if changes in myocardial images could result from alterations in left ventricular (LV) geometry independent of any change in tracer distribution. All dogs received 20 mCi of /sup 99m/Tc-labeled albumin microspheres (10-45..mu..) via the left atrium, after which control multigated, gated, and ungated myocardial perfusion images were obtained. Next, five dogs were sequentially imaged (1) during partial aortic occlusion to increase LV volume; (2) after release of the aortic occlusion; (3) after ligation of the coronary vasculature of the apex of the LV to produce regional dyskinesis; and (4) after nitroprusside induced hypotension to decrease ventricular volume. Only ligation and nitroprusside studies were done in the remaining five dogs. We gave 1.5 mCi of thallium-201 intravenously to two other dogs and obtained sequential ungated control, ligation, and nitroprusside images. At postmortem exam, tracer activity was equivalent at the apex and base for both microspheres and thallium. Nevertheless, partial aortic occlusion caused defects in the apex and anterior wall in four of five dogs. Coronary ligation caused new defects in eight of 10 dogs given microspheres and in both dogs given thallium. With nitroprusside, microsphere and thallium defects generally decreased in size. Gated images showedmore » that defects caused by ligation tended to be larger in end-systole than in end-diastole, while all partial aortic occlusion-induced defects were equal or greater in size in end-diastole compared with end-systole. These results indicate that changes in LV geometry or contraction pattern may cause defeccts on myocardial images without any change in tracer distribution.« less

Relation between computed zero-load aortic flow and cardiac muscle mechanics

Computed zero-load flow, q s ( t), is the expected aortic flow at zero aortic input impedance, thus eliminating the effect of afterload on ventricular ejection. It is computed from an equivalent model of the ventricle using the Fourier components of left ventricular (LV) pressure and aortic flow, q a ( t), of two consecutive beats with different input impedance produced by partial aortic occlusion. Actual q s ( t) may be measured during the first beat after transection of the aorta. In animal experiments computed q s ( t) was similar to the waveform and magnitude of actual q s ( t) and was sensitive to inotropic interventions. A relationship between zero-load flow and parameters of cardiac muscle mechanics is derived from the Thévenin equivalent model of the pumping function of the ventricle and the three dimensional force-velocity-length diagram. The present analysis indicates that aortic flow can be expressed as the difference of afterload-independent zero-load flow and externally-controlled afterload-dependent internal flow.

Sensitivity and afterload independence of zero-load aortic flow.

The computed zero-load flow is the expected aortic flow when the aortic pressure is zero, thus eliminating the effect of afterload on ventricular ejection. Zero-load flow was computed in 15 anesthetized dogs (sodium pentobarbital 25 mg/kg, iv) by studying the response of left-ventricular pressure or aortic pressure, and aortic flow to the change in aortic input impedance induced by partial snare occlusion of the aorta. The waveform and peak value of zero-load flow were computed from a theoretical model of the left ventricle and verified by measurements of aortic flow in the first beat after transection of the aorta. To study the sensitivity, changes of zero-load flow were computed under the enhanced inotropic state produced by isoproterenol (0.1 μg/kg/min), and under the depressed contractile state induced by propranolol (0.15 mg/kg). Administration of isoproterenol resulted in an increase in the peak zero-load flow by 143.9% (p<0.001), compared with a 50.6% increase (p<0.05) in peakdp/dt. The difference of the variations was statistically significant in a pairedt test. After injection of propranolol, peak zero-load flow decreased by 32.0% (p<0.005). Afterload independence of zero-load flow was studied by computing zero-load flow before and after increasing arterial pressure by partial aortic occlusion or injection of 5 mg methoxamine. After injection of methoxamine in denervated dogs, the peak zero-load flow increased by 11.2% (N.S.), while input resistance increased by 153% (p<0.025). The peak zero-load flow decreased by 8% (N.S.) after partial aortic occlusion, while cardiac output decreased by 26.7% (p<0.001). These results may suggest that the computed peak zero-load flow is an afterload independent index of the pumping capability of the left ventricle in the intact heart.

Distribution of myocardial blood flow measured by hydrogen polarography.

Distribution of myocardial blood flow was studied by polarographic recording of hydrogen desaturation in open chest dogs. Flow was measured during normal cardiac activity, reactive hyperemia following 60 seconds of coronary artery occlusion, and left ventricular hypertension produced by either partial supravalvular aortic occlusion or subvalvular outflow constriction. During normal cardiac function, blood flows in the subepicardium and subendocardium were approximately equal. Reactive hyperemia increased flow to both the subepicardium and subendocardium. Left ventricular hypertension decreased subendocardial flow relative to subepicardial flow in proportion to the degree of hypertension. Marked supravalvular obstruction with ventricular hypertension reduced subendocardial flow to two-thirds that of subepicardial flow. This decrease was further accentuated when the left ventricular end diastolic pressure was elevated.

Intestinal Blood Flow

Clearance of a parenchymal injection of xenon Xe 133 from the jejunum was used to asses changes in tissue perfusion produced by variations in superiorr mesenteric artery flow resulting from partial aortic occlusion. Disappearance of xenon from submucosa and muscularis was similar and reproducible. The biexponential function of the isotope clearanc exhibited a rapid initial component representing mean flow. Calculated xenon clearance rates, expressed as half-times for isotope disappearance and plotted as a function of decreasing superior mesenteric artery flow, were characteristically rapid for a broad range of superio mesenteric artery flows (90 to 600 ml/min). With reduction of superior mesenteric artery flow beyond 80 plus or minus 10 ml/min, tissue clearance of xenon was markedly prolonged. Adequate perfusion of the vascular compartments of the small bowel as measured by xenon clearance was maintained until 80% reduction of superior mesenteric artery flow.

Traumatic aneurysm of the abdominal aorta. Report of two cases and review of the literature.

Two cases of traumatic abdominal aortic aneurysm from blunt trauma are presented. Both were accompanied by partial aortic occlusion. In one case the aneurysm was of the dissecting variety; in the other it was a dilation proximal to a nearly total aortic obstruction. Both were successfully treated by operation, one using aortic resection with knitted Dacron graft replacement, and the other by abdominal aortic thromboendarterectomy. A review of the literature shows posttraumatic aneurysm to be rare in the abdominal aorta.

Secondary shock in the dog produced by total and partial aortic occlusion.

Summary1) A combination of hemorrhagic and partial aortic occlusion produces a controllable degree of hypotensive shock in the dog which closely resembles hemorrhagic shock. 2) The method provides an opportunity to study the effects of differential arterial perfusion of different body segments.