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Biomedical subjects

R F Bond

Publications and source records attributed to R F Bond.

At least 37 records · Page 2Linked to original sources
PubMed1985

Alpha 1- and alpha 2-adrenoreceptor relationships in SHRs during hypotension.

Previous studies have suggested that spontaneously hypertensive rats (SHRs) are less able to tolerate the cardiovascular stress of hemorrhagic hypotension than normotensive WKYs. The present studies were designed to determine whether or not this deficiency on the part of the SHRs is related to a genetically derived inappropriate balance between the alpha 1- and alpha 2-adrenoreceptors in the peripheral vasculature. To answer this question, SHRs were divided into untreated controls and experimental rats, which were pretreated with either the relatively specific alpha 1-antagonist prazosin or the alpha 2-antagonist yohimbine. In another series, the adrenal medullae were removed 2-3 days before hemorrhage. The data indicate that alpha 1-receptor blockade might offer some degree of protection to SHRs subjected to hemorrhagic hypotension, whereas inhibition of the alpha 2-adrenoreceptors proved detrimental. We conclude that the innervated alpha 1-adrenoreceptors play a more dominant role in SHR blood pressure regulation than the extrasynaptic alpha 2-adrenoreceptors but that these alpha 1-receptors are unable to maintain the compensatory vasoconstrictor response as effectively as the alpha 2-adrenoreceptors.

Adrenal Medulla↗
PubMed1985

Cardiovascular adrenoreceptor balance during hemorrhagic hypotension and shock.

The primary aim of this study was to examine the hypothesis that the ability of the cardiovascular system to compensate for hemorrhagic hypotension is controlled by a balance between the relative influence of the alpha 1 and extrasynaptic alpha 2 adrenoreceptors. Previous studies have implied that, although both receptors participate in the baroreceptor response to hypotension, only the extrasynaptic alpha 2 receptors are able to maintain the compensatory vasoconstrictor effort for a prolonged period of time. In each experiment two Sprague-Dawley rats were anesthetized and subjected to a modified Wiggers hemorrhagic shock protocol. One rat in each pair was pretreated with either 25 mg/kg of the cyclooxygenase inhibitor sodium meclofenamate or 0.5 mg/kg of the selective alpha 1 antagonist prazosin. The results indicate that neither drug interfered with the normal maximum compensatory effort as defined by the maximum blood loss (ie, reduced total vascular capacitance) when mean arterial pressure (MAP) was reduced to 30 mmHg by hemorrhage. In fact, when normalized for pre-hemorrhage MAP, it was apparent that prazosin, which lowered pre-hemorrhage MAP, may have actually improved the compensatory response. Sodium meclofenamate increased the time to reach the maximum compensatory effort (comp time), while prazosin increased the time to reach 20% uptake from the blood reservoirs (decomp time). Since both drugs enhanced the total time (comp + decomp) and both are known to interfere with alpha 1 function, these studies support the hypothesis stated above.

Animals↗
PubMed1985

Vascular adrenergic interactions during hemorrhagic shock.

The objective of this paper is to review the sequence of vascular events that follows severe hemorrhage. The initial cardiovascular imbalance is a fall in the volume/vascular capacity relationship that leads to reductions in cardiac output and mean arterial pressure (MAP). Peripheral sensors detect the fall in MAP and changes in blood chemistry that cause withdrawal of the normal inhibitory tone from the cardiovascular control centers in the central nervous system. The resulting increased sympathetic activity initiates a series of events that include stimulation of peripheral adrenergic nerves and the adrenal medulla. The magnitude of the compensatory vasoconstriction that follows is the net result of the interaction of the epinephrine (E) from the adrenal medulla and norepinephrine (NE) from the peripheral nerves on the peripheral vascular adrenoreceptors as well as other nonadrenergic mechanisms not discussed here (i.e., angiotensin endogenous opiates). By using pharmacological blocking agents, these adrenoreceptors have been subclassified as: innervated postsynaptic alpha 1; presynaptic alpha 2 (Ps alpha 2); and extrasynaptic alpha 2 (Es alpha 2) adrenoreceptors. The action of E and NE on the alpha 1 and Es alpha 2 receptors initiates the compensatory vasoconstriction, whereas action of these catecholamines on the Ps alpha 2 located on the presynaptic membrane inhibits further release of NE from peripheral nerve terminals, thereby reducing the effect of the innervated alpha 1 receptors. This autoinhibition together with a similar action by prostaglandin E on NE release is thought to be, at least in part, responsible for the vascular decompensation known to occur in the skeletal muscle after hemorrhage. Thus, one of the factors determining survival after hemorrhage may be related to the relative dominance of alpha 1 and Es alpha 2 receptors during the initial compensatory response.

Afferent Pathways↗
PubMed1985

Morphological differences in cutaneous and skeletal muscle vasculature during compensatory and decompensatory hemorrhagic hypotension.

PURPOSE: to determine if morphological differences exist between vasculature shown to decompensate, ie, skeletal muscle (SM) and vasculature that maintains the compensatory effort, ie, cutaneous (C). METHODS: dogs were anesthetized and subjected to a Wiggers hemorrhagic shock protocol. SM and C flows were monitored using electromagnetic flowmeters. Gracilis (SM) and saphenous (C) arterial segments were removed during: prehemorrhage control, compensation, and decompensation. Segments were fixed at in vivo intraluminal pressures. Both light and EM sections were made from each sample. RESULTS: During the compensatory phase, both SM and C showed signs of strong vasoconstriction. Even though the amount of endothelial folding was comparable, the C did and the SM did not sustain the vasoconstriction. Vascular diameters of the SM but not C increased during decompensation. Ultrastructural changes consisted of extreme folding of the internal elastic lamina (IEL) during compensation and subsequent flattening out of the IEL during decompensation in the SM but not the C tissues. Cell deformation, damage, and exfoliation were seen in both SM and C tissues. CONCLUSION: The data are consistent with the theory that SM vasculature, specifically endothelium, synthesizes an inhibitor of NE release, probably prostaglandins.

Animals↗
PubMed1984

Cardiovascular adrenoreceptor function during compensatory and decompensatory hemorrhagic shock.

Prior reports by Dr. Bond [1] have described the occurrence of an initial compensatory vasoconstriction followed by a decompensatory vasodilation response in animals that progress to irreversible shock induced by blood loss. Further analysis suggests that the secondary vascular decompensation is the result of sympathetic inhibition of adrenergic neurotransmission. The primary purpose of the present studies was to elucidate the roles of the alpha 1 and alpha 2 adrenoreceptors during initial compensatory and secondary decompensatory phases of hemorrhagic shock. This was accomplished by subjecting rat pairs to a modified Wiggers hemorrhagic shock protocol. One of these rats served as an untreated control (Rc) while the other (Re) received either an adrenergic antagonist or was bilaterally adrenal medullectomized 1-2 days prior to induction of shock. The adrenergic antagonists were: (1) propranolol, a nonspecific beta blocker; (2) phenoxybenzamine, a nonspecific alpha blocker; (3) tiodazosin, a specific alpha 1 blocker; and (4) yohimbine, a specific alpha 2 blocker. The results of these studies suggest that the beta receptors do not play a major role in either the compensatory or decompensatory response. Specific blockade of the alpha 2 adrenoreceptors accentuates decompensation by approximately 35%, while blockade of the alpha 1 adrenoreceptors may offer some degree of protection against the vascular decompensatory processes. These data support the conclusion that the extrasynaptic alpha 2 adrenoreceptors are better able to maintain the vascular compensatory effort than the alpha 1 adrenoreceptors.

Animals↗
PubMed1983

Cardiovascular-compensatory and decompensatory responses in rats anesthetized with pentobarbital compared to chloralose-urethane.

The data presented in these studies suggests that rats anesthetized with pentobarbital are better able to compensate for acute blood loss, but are less able to sustain the compensatory effort during hemorrhagic hypotension than rats anesthetized with chloralose-urethane. However, following reinfusion of shed blood the pentobarbital rats are better able to maintain their blood pressure.

Anesthesia↗
PubMed1983

Peripheral vascular adrenergic depression during hypotension induced by E coli endotoxin.

Previous studies support the concept that most vascular beds exhibit some degree of blood flow autoregulation (ie, vasodilation) in response to a fall in local perfusion pressure. However, when systemic pressure is reduced by acute hemorrhage, this vasodilation is converted to vasoconstriction. This response is due to extrinsic influences (ie, elevated adrenergic activity) which overwhelm the intrinsic autoregulatory response. The objective of the present investigation was to compare the regional vascular behavior in selected tissues (ie, skeletal muscle, skin, mesenteric and renal) during local hypotension and systemic hypotension induced by stepwise hemorrhage and endotoxin. Previously published data on local hypotension accomplished by gradual occlusion of the arterial inflow, and systemic hypotension induced by stepwise hemorrhage were compared to systemic hypotension induced by IV administration of 2 mg/kg E coli endotoxin. The pressure/vascular conductance data suggest the following: 1) Skeletal muscle, mesenteric, and renal vasculature respond to local hypotension by autoregulating while skin exhibits passive vasoconstriction; 2) all four vascular beds respond to hemorrhage by intense vasoconstriction; and 3) all four vascular beds respond to endotoxin by vasodilating. The data are compatible with the concept that endotoxin inhibits the extrinsic compensatory vasoconstrictor response to systemic hypotension in all of these vascular beds.

Adrenergic Fibers↗
PubMed1982

A review of the skin and muscle hemodynamics during hemorrhagic hypotension and shock.

The primary objective of this study was to compare the hemodynamic responses in a vascular bed known to exhibit decompensation (ie, skeletal muscle) with a nondecompensating bed such as the cutaneous vascular bed during systemic and local reductions in perfusion pressure induced by hemorrhage and sequential inflow arterial occlusion. The secondary objective was to examine the mechanisms which may be responsible for skeletal muscle vascular decompensation. Systemic hypotension was produced by a stepwise hemorrhage of 5 ml/kg body weight with 5-minute intervals between bleedings. The carotid sinus impact was examined during bilateral carotid artery occlusion. The intrinsic effects were evaluated during reductions in local perfusion pressure. The data show that skeletal muscle vasculature exhibits autoregulation but skin vasculature does not. Both vascular beds respond to acute hemorrhage by vasoconstriction; however, the vasoconstriction in the skin occurs as a result of increased plasma levels of catecholamines acting on alpha receptors with no neural component, whereas the vasoconstriction in skeletal muscle occurs as a result of both neural and humoral hyperactivity. The data presented also suggest that the skeletal muscle vascular decompensation occurring late in shock is the result of prostaglandin inhibition of a hyperactive sympathetic nervous system.

Animals↗
PubMed1981

Prostaglandin modulation of adrenergic vascular control during hemorrhagic shock.

This study was designed to evaluate 1) whether the initial compensatory skeletal muscle vascular constriction induced by hemorrhagic hypotension is primarily the result of increased adrenergic neural tone rather than circulating vasoconstrictor agents, and 2) whether the secondary skeletal muscle decompensatory vasodilation is caused by inhibitory action of prostaglandins on peripheral adrenergic nervous system. A constant-flow vascularly isolated double canine gracilis muscle preparation in which one muscle served as innervated control for the contralateral muscle was used. Dogs were subjected to standard stepwise hemorrhagic shock protocol. In series 1, perfusion pressures of control muscles were compared to denervated muscles with the result that innervated muscle perfusion pressures increased initially from 105 to 175 mmHg but subsequently fell significantly (P less than 0.05) to 147 mmHg. Only modest increases in perfusion pressures with no significant secondary fall were noted in denervated muscles. Series 2 compared innervated control perfusion pressures to pressures perfusing muscles pretreated with prostaglandin-synthesis inhibitor sodium meclofenamate (MCF). The MCF-treated muscle perfusion pressures rose to 260 mmHg where they remained without the secondary fall noted in control muscles. These data support the two hypotheses tested.

Animals↗
PubMed1981

Adrenergic neurotransmission failure in isolated canine jejunal arteries during hemorrhagic shock.

This study was designed to determine if the effective vascular smooth muscle population and/or effective adrenergic innervation density varies as the dog moves from compensatory to decompensatory hemorrhagic shock. Jejunal arteries with adventitia intact were removed during four different stages of shock and compared to nonshocked vessels. All vessels were placed in a tissue chamber filled with warm (37 degrees C) Krebs-Henseleit solution and bubbled with 95% O2 and 5% CO2 and exposed to (1) periarterial electrical stimulation and, (2) exogenously supplied norepinephrine (NE). The results are consistent with the hypothesis that the visceral vascular decompensation occurring as a result of prolonged hemorrhagic hypotension is caused by an adrenergic neuroeffector transmission failure.

Animals↗
PubMed1981

Adrenergic responses of gracilis arteries removed during hemorrhagic hypotension and shock.

Previous studies suggest that the gracilis vasculature responds to hypovolemic hypotension by constriction followed by vasodilation [Circ Shock 4:327, 1977; Circ Shock 6:43, 1979]. The objectives of the present study were to determine if the effective vascular smooth muscle population and/or adrenergic innervation density varies as the dog moves from compensatory into decompensatory shock. Gracilis arteries with adventitia intact were resected during four different stages of shock and compared to nonshocked vessels. All vessels were placed in a tissue chamber filled with warm (37 degrees C) Krebs-Henseleit solution and bubbled with 95% O2 and 5% CO2. Norepinephrine (NE) dose-response and periarterial electrical stimulation (ES) frequency-response studies were conducted. The maximum response to NE was not altered from control during either compensatory or decompensatory shock, but the maximum response to ES fell during compensatory and early decompensatory hypovolemic hypotension. The sensitivity of the innervated alpha receptors, as measured by the ES necessary to obtain a 50% maximal response (ES50), also fell below control during early decompensatory hypotension but returned to control values during early and late normovolemic shock, even though the sensitivity of the alpha receptors to NE (ED50) increased. These data support the suggestion that the skeletal muscle vascular decompensation occurring as a consequence of hemorrhage may be caused by a neuromuscular transmission failure.

Animals↗
PubMed1981

Adrenergic responsiveness of isolated saphenous arterial segments during hypovolemic hypotension and shock.

Previous studies from this laboratory suggest that cutaneous vasculature responds to hypovolemic hypotension by constriction as a direct result of catecholamine interaction with alpha-receptors (A.J.P. 212:488, 1967; A.J.P. 219:1210, 1970). The objectives of the present study were to determine if the effective smooth muscle population or adrenergic innervation densities varied as the dog progressively moves from reversible to irreversible hemorrhagic shock. Saphenous arteries were removed with adventitia intact during various stages of shock and placed in an isolated tissue chamber filled with warm (37 degrees C) Krebs-Henseleit solution bubbled with 95% O2 and 5% CO2. Norepinephrine (NE) dose-response curves and periarterial electrical stimulation (ES) response studies were conducted. The maximum responses to NE which we consider to represent an index of effective physiological smooth muscle population and ES (ie, effective physiological innervation density) decreased slightly during the progression from control Stage I to Stage III shock. The sensitivity of the innervated alpha-receptors as measured by the ES necessary to obtain a 50% maximal response (ES50) did not change during any stage of shock, indicating normal neural function. However, a significant reduction in NE ED50 from a control of 1.9 +/- 0.3 microM to 1.2 +/- 0.1 microM during early compensatory shock which persisted through early normovolemic shock indicated augmentation of alpha-receptor sensitivity. Signs of alpha-receptor desensitivation did not appear until late in the irreversible shock process when the NE ED50 increased to 3.9 +/- 1.1 microM.

Animals↗
PubMed1979

Correlation between skeletal muscle free fatty acid extraction and vascular decompensation during hemorrhagic hypotension.

The objective of this study was to determine whether or not a relationship exists between free fatty acid (FFA) extraction by skeletal muscle and onset of irreversible shock. Hind limb skeletal muscle vasculature of anesthetized dogs was surgically isolated from cutaneous tissue and subjected to a modified Wigger's hemorrhage shock protocol which was divided into five stages (I-V). Since the first signs of irreversibility began in stage II, this stage of hypovolemic hypotension was subdivided into IIa, IIb and IIc. Arterial and venous blood samples were taken during each stage for subsequent blood gas and FFA analysis. The data indicated that the onset of severe tissue ischemia and metabolic acidosis occurs concurrently with increased uptake of FFA and skeletal muscle vasodilation (decompensation). A possible physiological explanation for these observations could be related to an increased synthesis and release of PGE1. This agent has been shown by others to inhibit adrenergic neurotransmitter release causing loss of vascular tone.

Animals↗
PubMed1979

Correlation between skeletal muscle vascular decompensation and survival: roles of tissue ischemia and innervation.

A constant-flow, cross-perfused, vascularly isolated gracilis muscle preparation was used to examine the hypothesis that locally produced and released products of ischemic muscle metabolism are responsible for the vascular decompensation (vasodilation) reported to occur in late oligemic hypotension. Well-oxygenated donor arterial blood perfused recipient gacilis muscles at a constant flow rate of 5.2 +/- 0.5 ml/100 gm/min while the recipient animals were subjected to a modified Wigger's hemorrhage protocol. Arterial and venous blood gases taken across the gracilis muscle at regular intervals during the experiments verified adequate tissue perfusion. Of the thirteen studies reported, only ten shocked recipient dogs progressed to irreversible shock postreinfusion. This series was identified as the "recipient-irreversibly shocked group." The remaining three shocked animals recovered from the shock protocol and were labeled "recipient-reversibly shocked series." The initial response to blood loss in both groups was intense vasconstriction, with the greatest initial constriction occurring in the irreversibly shocked series. The three animals that survived the protocol were able to sustain this compensatory effort, but the ten that ultimately progressed into irreversible shock postreinfusion invariably demonstrated a significant loss of vascular tone during late oligemia (conductance rose from 43% to 63% of control). Thus evidence is presented which indicates decompensation during adequate tissue perfusion, or absence of ischemia. A strong correlation was also shown to exist between sustained compensatory vasoconstriction in the gracilis muscle, and survival. The suggestion is made that part of the loss of vascular tone may be related to prejunctional inhibition of adrenergic transmission or alpha-receptor fatigue, with a minor role being played by the vasodepressor products of local tissue ischemia.

Animals↗