Citations

Changes in cardiac output, stroke volume, and systemic blood pressure have been correlated with changes in muscle blood flow during the periods of initial transient and subsequent sustamed vasodilatation during intravenous infusion of epinephrine. In the initial phase blood pressure decreased slightly; forearm blood flow increased by 308%, cardiac output by 50%, and stroke volume by 10%. During the sustained phase the systolic blood pressure increased; corresponding increases for the other measurements were 87, 47, and 25%, respectively. The lack of correlation between these changes in cardiac output and forearm blood flow suggests that in the transient phase vasodilatation does not occur simultaneously in all muscle groups. Stroke volume makes a greater contribution to the increased output during the sustained phase. Submitted on May 29, 1961

Cardiac output was measured simultaneously with blood flow in hand and forearm in eight healthy subjects before and during body heating. The heating was carried out by immersing the feet and legs in water at 44 C. and wrapping the body with blankets. After 50 min of heating the oral temperature had risen to between 99.5 and 100.8 F. The cardiac output had increased by 1.9—4.5 (mean 3.3) liters/min, mainly because of an increase in heart rate. The blood flow through the fingers increased rapidly to reach maximal values soon after heating started, whereas the forearm blood flow, like the cardiac output, increased gradually throughout the heating period. Since the increase in limb blood flow is confined to the skin vessels and since there is no evidence that flow to the internal organs is increased, the total increase in skin flow amounts on the average to 1.8 liters/m2/min. Submitted on June 2, 1961

Dilution curves were obtained by sampling from the aortic root or a carotid artery after injection of indicator dye into the pulmonary artery in five dogs at rest and during exercise. On four occasions a common sampling system was used; curves were recorded simultaneously and in parallel from a cuvette oximeter assembly with a slow dynamic response and from a phototube densitometer with a fast response. In the fifth study, separate slow and fast sampling systems were used interchangeably with the two detecting instruments. Values for cardiac output were similar with the two instruments; maximal divergence for any single observation was 9% from the line of identity. The aortic root is a favorable sampling site for such a comparison, since extrapolation of the dilution curves is usually unnecessary. Under these conditions measurement of cardiac output was not influenced by the dynamic response characteristics of the sampling-detecting-recording system. When mean transit times of the respective curves were corrected for instrumental delay, there was also satisfactory agreement in values for “central” blood volume. However, since the time correction for the densitometer is relatively small, it is the preferable instrument for this measurement. Submitted on October 24, 1960

With the use of a strain-gauge plethysmograph, the effect of a brief (0.3 sec) contraction of the forearm muscles on forearm blood flow has been studied in eight healthy adults. An increase in flow due to dilatation of the muscle vessels could be detected within a second after the completion of the contraction. This increase was proportional to the strength of the contraction. The blood flow was maximal immediately and decreased rapidly. A second contraction of the same magnitude made during the period of increased flow caused an additional increase in flow. The maximal increase in flow caused by a strong brief contraction was only about 25% of that recorded after strong repeated rhythmic contractions or a sustained contraction. Cervical sympathectomy did not change these findings, indicating the local nature of the response. Since breathing oxygen failed to reduce the dilatation for a given strength of contraction, it is unlikely that oxygen lack was the stimulus for vasodilatation. The oxygen saturation of blood that drained the muscles could not be determined accurately immediately after contraction because at this time, muscle venous blood was contaminated by venous blood from the skin. exercise-induced vasodilatation; local mechanism of vasodilatation; venous O2 saturation during muscle contraction; brachial arterial pressure during vasodilatation; speed of muscle vasodilatation Submitted on May 8, 1963

Ten consecutive time trials were run at 2-day intervals by six racing greyhounds over a 5/16-mile track. Cardiac denervation was then performed on four dogs, and a sham operation that included removal of the pericardium was performed on two dogs. After cardiac denervation, one dog died and another was rejected from the study because of a massive intrathoracic hemorrhage. The time trials were repeated with the addition of telemetry of the heart rate in the four survivors. There was no significant difference between mean preoperative and postoperative race times in the control group. The mean postoperative running speeds of 33.6 and 33.3 mph in the denervated group, although representing a significant slowing of 1.1 and of 2.1 mph, respectively, from preoperative values, indicate the adequate manner in which the denervated heart meets the circulatory demands of maximal running effort. cardiac output; heart rate and exercise Submitted on March 11, 1964

Normal subjects were studied to determine whether exercise of the muscles of one forearm causes changes in venous tone in that forearm by some local mechanism. Forearm venous pressure-volume relationships and the pressure in “isolated” vein segments were unchanged after exercise of forearm muscles. Following venous occlusion, the forearm volume increases and reaches a plateau later than forearm venous pressure. This delayed volume change increased with increasing venous filling rate regardless of whether this was accomplished by exercise or by other means. Thus, the local mechanism which dilates resistance vessels in active muscles does not seem to change the contractile state of the muscle in the capacity vessels. The viscous properties of the venous wall, however, act to damp the volume oscillations in intervals between muscular contractions when arterial inflow and venous filling rate are high. The ratio between initial rate of rise in forearm venous pressure and volume following venous occlusion could not be used as an index of active changes in tension of the smooth muscle of the capacitance vessels. strain-gauge plethysmography; isolated vein segments; venous response to varying filling rates; venous response to local exercise; veins and exercise Submitted on November 16, 1964

Venous occlusion plethysmography is a simple but elegant technique that has contributed to almost every major area of vascular biology in humans. The general principles of plethysmography were appreciated by the late 1800s, and the application of these principles to measure limb blood flow occurred in the early 1900s. Plethysmography has been instrumental in studying the role of the autonomic nervous system in regulating limb blood flow in humans and important in studying the vasodilator responses to exercise, reactive hyperemia, body heating, and mental stress. It has also been the technique of choice to study how human blood vessels respond to a variety of exogenously administered vasodilators and vasoconstrictors, especially those that act on various autonomic and adrenergic receptors. In recent years, plethysmography has been exploited to study the role of the vascular endothelium in health and disease. Venous occlusion plethysmography is likely to continue to play an important role as investigators seek to understand the physiological significance of newly identified vasoactive factors and how genetic polymorphisms affect the cardiovascular system in humans.

Human umbilical artery was perfused with Krebs-Ringer bicarbonate-glucose medium at 37 C and pH 7.4. An increase in transmural pressure elicited a vasoconstriction. The artery wall contained no significant amount of norepinephrine, which supports the anatomic evidence of absence of nerve supply. Thus, the response to stretch is due to a smooth muscle cell-borne positive feedback mechanism. The myogenic reflex could still be elicited at 44 C but was reversibly abolished by cooling to 4 C. It was reversibly abolished in the absence of calcium. K2SO4-Ringer solution (50 mm in K) markedly increased the tone of the artery after an initial vasodilatation and induced rhythmicity when the perfusion pressure was increased. Bradykinin, 5-hydroxytryptamine, and angiotensin caused vasoconstriction when the artery no longer responded to stretch. Stretch could induce vasoconstriction when angiotensin no longer elicited a response because of tachyphylaxis. The stretch reflex was not blocked by phenoxybenzamine which suppressed the response to 5-hydroxytryptamine. Tachyphylaxis was not observed with bradykinin; the effect of bradykinin was not blocked by phenoxybenzamine.

Following attempted denervation of the heart by the technic of regional neural ablation, dogs with incomplete cardiac denervation were shown to have the same supersensitivity to l-norepinephrine as dogs in which the denervation of the heart was complete. Dogs with chronic bilateral stellate ganglionectomy or those pretreated with reserpine had cardiac acceleration in response to the administration of tyramine or to stimulation of the stellate cardiac nerves, but did not demonstrate supersensitivity to l-norepinephrine. No supersensitivity was seen in dogs with chronic bilateral cervical vagotomy. Excision of the right stellate and caudal cervical ganglia and the immediately adjacent right vagus nerve resulted in supersensitivity to l-norepinephrine. In these animals cardiac acceleration resulted from stimulation of the left stellate cardiac nerves or from the administration of tyramine. The supersensitivity was lost after excision of the sinoatrial node. It is concluded that one can uniquely denervate the sinus node and that dogs so treated will develop supersensitivity to l-norepinephrine despite the presence of functional sympathetic nerves to the rest of the heart.

In three normal dogs and in six dogs with cardiac denervation, there was a rapid increase in cardiac output (electromagnetic flowmeter) from the start of exercise. The denervated group showed an average delay of 25 sec in reaching plateau values of cardiac output and a deficit of 18% in the accumulated flow over the first minute of running; augmentation of output was due principally to a rapid increase in stroke volume since acceleration of heart rate was slow. In normal dogs, the augmentation of output came from a rapid increase in heart rate. The steady-state values for cardiac output and oxygen consumption were similar in the two groups as was the pattern of oxygen consumption in the first minutes of exercise and the manner in which the oxygen debt was repaid. This suggested that the denervated dogs extracted more oxygen from the circulating blood in the first moments of running. The changes with exercise in aortic blood pressure were similar in the two groups.