SUMMARY Measurements of cerebral spinal fluid pressure, arterial pressure, and internal carotid artery blood flow were obtained in a series of patients during a Valsalva maneuver. During straining (phase II), an 11% reduction in mean arterial pressure was associated with a 21 % decrease in internal carotid flow from control values; and following release (phase IV), the 19% increase in mean arterial pressure produced a 22% increase in internal carotid artery flow. Perfusion pressure computed as the mean arterial pressure minus cerebral spinal fluid pressure and internal carotid artery blood flow were used to calculate an index of cerebral vascular resistance. The data indicate that a modest but significant decrease in vascular resistance occurred during phases II and III followed by return to control levels during phase IV. These changes in vascular resistance were not rapid enough or of sufficient magnitude to maintain constant cerebral perfusion during the Valsalva maneuver. Stroke Vol 15, No I, 1984 THE PRECISION with which cerebral vascular blood flow can be maintained at a constant value during rapid changes in perfusion pressure has not been defined in man primarily due to the methodologic limitations encountered in measuring phasic cerebral blood flow. Quantitative measurements of phasic internal carotid artery flow have been obtained in man with an electromagnetic flowmeter and can be used as an index of cerebral flow.2 -3 The Valsalva maneuver is associated with marked changes in arterial pressure and thus, can be used to study the effects of rapid changes in arterial pressure on cerebral blood flow. 9 The purpose of this study was to measure the internal carotid artery blood flow and to compute for the first time the changes in cerebral vascular resistance which occur accompanying a brief Valsalva maneuver in a series of nine patients. MethodsNine male patients were studied who had been hospitalized on the Neurosurgical Section of the Veterans Administration Hospital, Durham, North Carolina. In each patient subtotal resection of a supratentorial malignant brain tumor had been carried out from 10 to 20 days previously. The data described in this report were obtained during exposure of the carotid vessels so that an antitumor agent (S-l 12, a chlorethylthioacetamide, Sfxg/kg) could be infused directly into the internal carotid artery. This drug was given immediately after the completion of the studies described. The informed consent of each patient was obtained.* At the time of study, the patients were alert and showed no major neurological deficits. The cerebrospinal fluid (CSF) pressure was less than 250 mm H 2 O. *This investigation was carried out under the procedures currently applicable for human investigation. Before the surgical procedure the patients were premedicated with 50 mg of meperidine and 25 mg of promethazine. Local anesthesia was accomplished with injections of lidocaine. The common carotid artery and proximal portions of both the internal and external carotid arteries were exposed, ...

The pressure gradient technique was used to evaluate effects of respiration on left ventricular stroke volume in 22 patients: 11 normal patients; eight patients with airway obstruction; and three patients with pericardial tamponade. In normals, stroke volume, systolic pressure, and pulse pressure fell an average of 7, 3 and 11% (P < 0.01), respectively, during inspiration. In patients with airway obstruction, these parameters decreased by 25, 12 and 23% (P < 0.001), respectively. After breath-holding, stroke volume also fell immediately with the onset of inspiration in both groups. These results are consistent with a reduction in left ventricular filling during inspiration as the factor primarily responsible for the fall in stroke volume. In patients with pericardial tamponade, variations in left ventricular stroke volume, systolic pressure and pulse pressure were related to:(1) an immediate fall in stroke volume with the onset of inspiration; and (2) a subsequent increase in stroke volume presumably due to an inspiratory increase in right ventricular stroke volume. Additional Indexing Words: Ventricular functionPericardial tamponade Pulsus paradoxus Obstructive lung disease T HE INFLUENCE of respiration on left ventricular function has been studied since the technique of cardiac catheterization in man was perfected. Lauson, Bloomfield and Cournand found that the systemic arterial systolic, diastolic and pulse pressures were lowest during inspiration, when intrapleural pressure is least, and highest at the peak of expiration when intrapleural pressure is greatest.' These workers postulated that this finding resulted in part from transmission of the respiratory From the

A B S T R A C T Regional myocardial blood flow during both control conditions and ischemia-induced vasodilatation was studied in eight chronically instrumented awake dogs. Seven of these animals had coarctationbanding ofthe ascending aorta performed at 6 wk of age, and the other dog had congenital subvalvular aortic stenosis. The mean left ventricular weight for the group was 157±7.6 g, and the left ventricular body weight ratio was 8.76+0.47 g/kg. None ofthe animals exhibited signs of congestive heart failure.During the control state, the mean left ventricular systolic pressure was 249+12 mm Hg and the left ventricular end-diastolic pressure was 11.5±0.5 mm Hg. The aortic diastolic pressure was 74±6 mm Hg. Mean left circumflex coronary artery blood flow was 71±6 cm3/min. In the animals with coarctation-banding, 52±6% of the flow occurred during systole. In the dog with congenital subvalvular aortic stenosis, 5% of the coronary flow was systolic. Mean transmural blood flow during resting conditions was 0.97±0.08 cm3/min per g, and the ratio of endocardial to epicardial flow (endo/epi) was 0.88±0.07. During reactive hyperemia, the mean transmural blood flow increased to 3.5±0.30 cm3/min per g; however, the endo/epi decreased to 0.52±0.06.These studies document a difference in transmural blood flow distribution between the normal and the hypertrophied left ventricle: during resting conditions, in the normal ventricle, the highest flow occurs in the endocardial layer, whereas in the hypertrophied ventricle, the highest flow is in the middle layers with the endocardial flow less than the epicardial flow.

Compliance of the left atrial chamber was estimated with and without the appendage intact in six isolated canine left atria. Pressure-volume determinations were measured over a range of 5-30 mmHg for the whole left atrium and were repeated with the appendage excluded. The slope of the pressure vs. normalized volume data for the left atrium without the appendage (10.45 +/- 0.87) was significantly greater (P less than 0.01) than with the appendage intact (4.10 +/- 0.72). These data suggest that the left atrial appendage is more compliant than the remaining left atrium. Assuming that this relationship remains in vivo, the left atrial appendage may play an augmented role in maintaining hemodynamic function when filling pressures are elevated.

Regional myocardial oxygenation was assessed during partial and complete coronary artery occlusion using near

Myocardial oxygenation may be altered markedly by changes in tissue blood flow. During brief ischemia and reperfusion produced by transient occlusion of the left anterior descending artery in 10 open-chest dogs, changes in the oxygenation of tissue hemoglobin (Hb) plus myoglobin (Mb) and the oxidation-reduction (redox) state of mitochondrial cytochrome aa3 were monitored continuously using near-infrared spectroscopy. The nondestructive optical technique indicated that coronary occlusion produced an abrupt drop in tissue oxygen stores (tHb02 + Mb02), tissue blood volume (tBV), and the oxidation level of cytochrome aa3. Changes in the cytochrome oxidation state were related inversely to transmural collateral blood flow within the ischemic region (r = 0.77) measured with radiolabeled microspheres. Furthermore, there was a direct relationship (r = 0.91) between collateral blood flow and the tissue level of desaturated Hb and Mb (tHb + Mb). Reperfusion after 2 min of ischemia led to a synchronous overshoot of baseline in coronary flow and tBV followed by supranormal increases in tHb + Mb02 and the oxidation level of cytochrome aa3. The tHb + Mb level increased transiently during reperfusion. This response correlated inversely with collateral flow during ischemia (r = 0.91). Accordingly, the time required to reach peak tHb + Mb levels was shortest in dogs with high collateral flows (r = 0.75). Thus collateral blood flow partially sustains myocardial oxygenation during coronary artery occlusion and influences tissue reoxygenation early during reperfusion.

A reproducible model for the production of moderate to severe concentric left ventricular hypertrophy has been developed in this laboratory. Coarctation-banding of the ascending aorta was performed successfully in 10 puppies. There were no late deaths related to aortic rupture, and in the dogs surviving for 1 yr no evidence of congestive heart failure was present. A second operative procedure was performed in seven dogs for chronic instrumentation, and all survived. Severe supravalvular aortic stenosis with a marked peak systolic pressure gradient was noted in each dog. Postmortem examination revealed a substantial increase in left ventricular mass and in the ratio of left ventricular to body weight.

Studies were conducted to determine the effects of adenosine on transmural myocardial blood flow distribution. Both maximal and submaximal vasodilatory doses of adenosine were infused into awake resting dogs chronically instrumented with coronary flow probes and aortic and left atrial pressure catheters. Radioactive microspheres (8-10 micron) were used to determine regional coronary blood flow. Four experimental protocols were evaluated: 1) the effects of maximal (1.00 mg . kg-1 . min-1) as well as submaximal (0.45 mg . kg-1 . min-1) vasodilatory levels of adenosine, 2) the dose-response characteristics of adenosine, 3) the dose-response characteristics of dipyridamole, and 4) the effects of adenosine in the presence of an increased arterial PO2. The data indicate that maximal vasodilatory doses of adenosine have little effect on the endocardial-to-epicardial blood flow ratio, whereas submaximal doses result in a marked preferential endocardial perfusion. This relative increase in endocardial perfusion was not altered by hyperoxia. Dipyridamole, in submaximal doses, produced a similar preferential flow to the endocardial layer. These data demonstrate that the vasodilator reactivity to adenosine infusion is greater in the endocardial layer,