What Is High Enough? Elevated NT-pro-BNP in Decompensated Paroxysmal Supraventricular Tachycardia.

Since the late 1980s, elevated atrial natriuretic peptide (ANP) was considered the cause of brisk diuresis in adult patients with paroxysmal supraventricular tachycardia (PSVT). Pro-brain natriuretic peptide (pro-BNP) and related molecules, e.g., N-terminal pro b-type natriuretic peptide (NT-pro-BNP) are known biomarkers of heart failure in adult patients from many causes with probable relevance in children. Perhaps, pro-BNP or related molecules such as NT-pro-BNP are useful in the management of PSVT in infants, thus hastening treatment in children who may otherwise significantly decompensate. Case series of one infant and two neonates presenting with cardiogenic shock and evidence of heart failure are presented. Cardiac monitoring or electrocardiogram (ECG) confirmed the presence of PSVT. Adenosine was administered resulting in successful chemical cardioversion with each case. Significantly elevated NT-pro-BNP levels correlated with heart failure prior to cardioversion. In each case, patients were discharged home with lower NT-pro-BNP levels and maintenance with a ß-blocker. Due to documented relationships between elevated pro-BNP level and heart failure in adults, the authors measured the related biomarker NT-pro-BNP in each case, as the relationship could be similar in pediatric PSVT. Based on our experience with children in acute heart failure from other causes, NT-pro-BNP can increase to potentially extreme levels in infants. It appears to correlate with clinical signs of insufficient cardiac output, such as tachycardia, respiratory distress, and moribund appearance. Indeed, in the case series, extremely high NT-pro-BNP values were obtained when the patients appeared moribund from decompensated PSVT. The question arising from these observations is: At what level of elevated NT-pro-BNP, would patients be identified for cardioversion prior to appearance of other signs and symptoms? For each patient within the case series, NT-pro-BNP levels of approximately 20,000 pg/mL were indicative of decompensated heart failure, which was subsequently confirmed by examination of the patient. Further investigation is needed to determine the clinical significance of NT-pro-BNP and related peptides in pediatric patients with PSVT and intermittent PSVT. However, the possibility exists that an increase in NT-pro-BNP and related peptides could be a biomarker for cardiac decompensation after prolonged or intermittent PSVT, thereby shortening the time of diagnosis and intervention, and hence, potentially preventing morbidity, mortality, and extended hospitalization. Additional evidence-based research would help provide biomarker information during PSVT allowing practitioners to more objectively analyze risks.

Psychobiological effects of carbohydrates.

The authors studied whether the fatiguing effects of eating lunch are greater for carbohydrate-rich meals than for other meals, and related the time course of behavioral change to plasma glucose, insulin, and amino acids. On different occasions, in counterbalanced order, normal women (N = 7) fasted overnight, ate a standard breakfast, and at lunch either continued to fast or ate a high-carbohydrate, low-protein meal; a hedonically similar meal containing both carbohydrate and protein; or a high-protein, low-carbohydrate meal. Meals were isocaloric and equated for fat content. Only the carbohydrate meal significantly increased fatigue, which could not be attributed to hypoglycemia because plasma glucose remained elevated. Fatigue began approximately, when the carbohydrate meal elevated the plasma tryptophan ratio but ended even though the ratio remained elevated. Fatigue after a high-carbohydrate lunch could not be explained by reactive hypoglycemia or sweet taste, and could partially be explained by the hypothesis that fatigue parallels an elevation of the tryptophan ratio.

Pain threshold changes induced by acute exposure to altered ambient temperatures.

Our previous findings that the degree of endotoxin-induced hypotension in the dog is inversely related to ambient temperature (19 degrees through 30 degrees C) and that only increased doses of naloxone are effective at 19 degrees C suggested that opioid activity is also influenced by ambient temperature, increasing in the cold and decreasing in the warm. Others have reported increases in plasma beta-endorphin in rats with acute exposure to both 5 degrees and 36 degrees C. In this study we measured changes in pain thresholds after both acute and chronic exposures to lesser alterations in ambient temperature as a potentially more sensitive index of changes in central opioid activity. Compared to 24 degrees C there was a marked increase in pain threshold with acute exposure to 10 degrees C and marked decreases at 30 degrees and 35 degrees C. A slight decrease occurred after 30 minutes but not 60 or 120 minutes at 19 degrees C. All acute changes disappeared three hours after the animals had been returned from the altered ambient temperature to 24 degrees C. No changes were observed after six days chronic exposure to 10 degrees or 30 degrees C. These findings suggest that moderate, acute changes in ambient temperature can produce inversely related, adaptable alterations in central opioid activity.

Inhibitory effects of cerebellar lesions on respiration in the spontaneously breathing, anesthetized cat.

Acute cerebellectomy depressed spontaneous respiration in cats anesthetized with chloralose-urethane. After cerebellectomy there was an increased interbreath interval (TTOT) accompanied by increased inspiratory and expiratory durations (TI and TE, respectively). However, the change of TE exceeded that of TI so that TI/TTOT decreased. Tidal volume (VT) and mean inspiratory flow (VT/TI) were not affected. No respiratory variable was significantly altered when cerebellectomy was performed subsequent to bilateral vagotomy. Bilateral lesions of the rostral fastigial nuclei (FN) in cats with intact vagi also caused a reduction in ventilation due to increased TTOT. In this case TI and VT/TI increased, but VT and TI/TTOT remained unchanged. Bilateral control lesions that usually included portions of the dentate nuclei did not influence respiration. The results suggest that in the anesthetized cat the cerebellum tonically excites respiratory centers controlling respiratory rate and the termination of inspiration. A part of this influence may be mediated by the rostral FN. In addition, vagal input appears to be important in the expression of the cerebellar influence on spontaneous respiration.

Bilateral lesions of the fastigial nucleus prevent the recovery of blood pressure following hypotension induced by hemorrhage or administration of endotoxin.

The present studies were undertaken to determine if bilateral lesions of the fastigial nuclei of the cerebellum would impair the recovery and maintenance of mean arterial blood pressure during hypotension caused by hemorrhage or administration of endotoxin. We had shown previously that cerebellectomy would produce such an impairment, and the fastigial nuclei were implicated as the specific area involved due to the known pressor response observed when they are stimulated electrically. Chloralose-anesthetized dogs were made hypotensive by administration of E. coli endotoxin or hemorrhage to 50 mm Hg and observed over the subsequent 3 h. Dogs with fastigial nucleus lesions had a significantly lower mean arterial pressure during both the recovery and maintenance phases when compared with intact animals under both hypotensive protocols. In the hemorrhage study, a significant number of lesioned animals died whereas none of the controls died. Lesion of the fastigial nuclei produced an impairment similar to that seen with cerebellectomy. It is concluded that the fastigial nuclei play an important role in the recovery of blood pressure following a hypotensive episode.

The effects of chronic administration of naltrexone on appetite and water exchange in rats.

The effects of chronic administration of naltrexone (200 microgram/kg/hr) on appetitive behaviors and renal water and electrolyte excretions were studied in rats. Naltrexone reduced food and water intake, the renal excretions of water and electrolyte excretions were studied in rats. Naltrexone reduced food and water intake, the renal excretions of water and electrolytes, and osmolar clearance. No changes in plasma levels of electrolytes, plasma and urine Na+-K+ ratios, hematocrit ratio, plasma osmolality, the clearances of K+ and Na+, and the reabsorption of solute free water were found. The changes in appetite were compensated for by appropriate changes in renal excretions, resulting in no change in electrolyte balance or water exchange. These observations are discussed in relation to current theories of the role of endorphins in appetite control.

Electrocardiography and postextrasystolic potentiation: utilization of the two methods to predict postrevascularization segmental myocardial function.

We previously reported that postextrasystolic potentiation (PESP) is a useful predictor of changes in systolic wall function (SWF) following coronary revascularization. In the current study we analyzed ECG changes related to corresponding myocardial segments to determine their correlation with PESP and SWF. We found: (1) The PESP response in a jeopardized segment was a valid predictor of improved SWF even when Q waves, ST-segment changes, or T-wave changes were present. (2) However, when Q waves were present in two or more of the corresponding leads, positive PESP was less likely to be observed. (3) Thus Q waves in two leads predicted the least postrevascularization improvement. (4) Segments with no corresponding Q-wave postrevascularization usually improved SWF. (5) Furthermore, a continuum of responsiveness to PESP was found, ranging from T-wave changes, ST-segment changes to Q-wave changes, indicating dissociation between electrical and mechanical events. In conclusion, the ECG together with PESP provide good predictive information relative to the efficacy of revascularization. PESP is a more valuable predictive indicator. ECG alone may be of value in that the occurrence of Q waves in two or more corresponding leads predicts a low probability of improved SWF. Further studies are indicated to investigate the dissociation between electrical and mechanical events.

Use of a programmable calculator for rapid, low-cost processing of echocardiographic records.

A comparative study was performed to determine the accuracy of a programmable calculator with supplemental digitizer in echocardiographic analysis. Twenty separate measurements were collected per heart beat from five different dogs, taking five heart beats from each dog. The measurements were made by an echocardiographic technician (ET), echocomputer (EC), and by a programmable calculator (HP). In a triple comparison (ET-HP, ET-EC, HP-EC) there were no significant differences in the values obtained, suggesting that the programmable calculator can provide a highly accurate and rapid means of processing echocardiographic measurements, thereby providing the advantages of the echocomputer without the cost of such a device.

A citywide evaluation of identification of risk factors for cardiovascular disease in emergency department patients complaining of chest pain.

The local division of the American Heart Association in Lubbock, Tex, conducted a cooperative study involving all three local hospitals to assess how effectively risk factors for cardiovascular disease are identified in patients presenting in the emergency departments with a complaint of chest pain. The charts of 250 consecutive patients with chest pain were reviewed for risk factors identified by the triage nurse and by the emergency department physician or the attending physician or both. Although the rate at which risk factors were identified was good, identification was neither complete nor comprehensive. Comparison with statistics for the general population showed that some risk factors were over-reported, while others were markedly underreported. Each of the three specialties of health care professionals stressed different risk factors, and having all three involved markedly increased the level of identification. The data provide guidelines for improving risk factor identification, and the study led to the formation of strategic alliances among the different hospitals and health care professionals that should help improve secondary prevention of cardiovascular disease within the community.

Regulation of adrenal blood flow: response to hemorrhagic hypotension.

Adrenal blood flow was measured during hemorrhagic hypotension in pentobarbital-anesthetized dogs using the radioactive-microsphere technique. A decrease in adrenal vascular resistance occurred during hemorrhage that was sufficient to maintain adrenal blood flow at prehemorrhage levels even with a decrease in mean arterial blood pressure (MABP) to as low as 50 mmHG. Blockade of alpha- and beta-adrenergic receptors, H1- and H2-histamine receptors, and prostaglandin synthesis all decreased resting adrenal blood flow. However, blood flow did not decrease further with hemorrhage subsequent to these interventions. Neither cholinergic blockade (muscarinic) alone nor ganglionic blockade subsequent to cholinergic blockade changed adrenal blood flow. However, ganglionic blockade alone increased adrenal blood flow. Hemorrhage subsequent to hypophysectomy also did not change blood flow to the adrenal. These data suggest that the maintenance of adrenal blood flow during hemorrhagic hypotension to 50 mmHg MABP is independent of the autonomic nervous system, prostaglandin synthesis, histamine receptors, or an intact pituitary-adrenal axis, even though all of these systems do influence adrenal blood flow.

Stimulating fastigial nucleus pressor region elicits patterned respiratory responses.

Electrical stimulation of the ventromedial region of the rostral fastigial nucleus (FN) in the cat produced marked quantifiable changes in respiration that were highly correlated with the concurrently elicited cardiovascular responses. The threshold- and stimulus-response curves were very similar for the two responses. Stimulation at relatively low frequencies produced increases in respiratory rate at all active sites. At approximately half the sites biphasic responses were observed with increases in stimulus frequency. These were characterized by a transient period of apnea beginning with onset of the stimulus, followed by an increased respiratory rate. At the remaining sites respiratory rate increased at all stimulation frequencies tested. Inspiratory duration decreased, and mean inspiratory flow increased. Tidal volume was not significantly altered. Similar changes were also observed when the pressor response was blocked by phenoxybenzamine. These observations, together with the frequent demonstration of expiratory-to-inspiratory and inspiratory-to-expiratory phase switching with short-burst stimulation, suggest that the FN can influence a respiratory central pattern generator. Based on these findings, a possible role for the FN in integrating cardiovascular and respiratory responses is suggested.

Influence of central nervous system on arterial pressure during endotoxin shock.

Some investigators have suggested that the hypotensive effects of endotoxin are exerted at the level of central nervous system (CNS). Others feel the effects are exerted peripherally and that the CNS is involved in the regulation of the cardiovascular system during the shock state. Still other data suggest that endotoxin shock is entirely a peripheral phenomenon. The present study used ventriculocisternal perfusion of endotoxin, a pretrigeminal brainstem transection, two midcollicular decerebrate preparations, and Cushing's reflex to investigate the involvement of the CNS during endotoxin shock. The results suggest the following: 1) endotoxin perfused centrally at a concentration equivalent to the maximum obtainable after peripheral injection will not alter mean arterial pressure (MAP); 2) either the forebrain is not involved in the MAP response or the remaining regions can compensate for its absence; and 3) Cushing's reflex will block the initial endotoxin-induced hypotension.

Gender and propranolol-ethanol interaction.

The in vitro effect of propranolol, a beta-receptor blocking agent, on specific activity of hepatic alcohol dehydrogenase (L-ADH) and aldehyde dehydrogenase (L-ALDH) was studied in the male and in the female rat. The presence of propranolol, in the dose range of 3 x 10(-4) M to 10(-3) M concentration in the reaction mixture noncompetitively inhibited female but not male L-ADH. Conversely, significant enhancement of mitochondrial but not cytoplasmic L-ALDH occurred in the presence of propranolol, between 10(-3) M and 10(-5) M concentration, in both sexes. The alteration of hepatic ethanol and acetaldehyde metabolizing enzymes by propranolol suggest both gender difference and possible contraindication of use of this drug in alcoholic patients.

Effect of altitude exposure on thermoregulatory response of man to cold.

The thermoregulatory responses to 10 degrees C (for 3 h) were investigated in 1) 12 natives from sea level (lowlanders) at 150 m, and on arrival at 3,350 and 4,340 m; 2) 6 of these during a 6-wk sojourn at 4,360 m, and on return to sea level; and 3) 5 natives from each of the two altitudes (highlanders) in their respective habitat, and after descent to 150 m. The cold-induced increase in the rate of O2 consumption (Vo2) of the lowlanders was significantly smaller at both altitudes than at sea level. It did not recover substantially during the 6 wk at altitude, but was restored to its initial rate on return to sea level. By contrast, visible shivering activity was augmented on arrival at altitude. It persisted throughout the 6 wk there, but was greatly depressed on return to sea level, despite the increased Vo2. Mean skin temperatures (Tsk) stabilized in the cold at significantly higher values at altitude. Rectal temperature (Tre) decreased similarly at all altitudes. Vo2 of the highlanders in the cold was significantly greater at sea level than at their resident altitudes, although shivering activity was less intense; Tsk stabilized at significantly lower levels at 150 m than at either altitude. These results indicate that altitude exposure reduces the calorigenic response of man to cold, and that this effect is not moderated by acclimatization to altitude, yet is reversible immediately on descent to sea level. The component of cold thermogenesis which appeared to be reduced by altitude exposure was nonshivering thermogenesis rather than visible shivering.

Cerebellar lesions alter autonomic responses to transient isovolaemic changes in arterial pressure in anaesthetized cats.

In previous studies, bilateral lesions of the rostral fastigial nucleus (rFN) of the cerebellum impaired recovery of mean arterial pressure (MAP) after many forms of hypotension. This study examined effects of cerebellar lesions on baroreflex responses during transient, isovolaemic, non-orthostatic changes in MAP in anaesthetized cats. Bilateral rFN lesions did not alter the rate or extent of fall in MAP induced by nitroprusside, but reduced by 39% the reflex increase in heart rate per unit decrease in pressure (delta HR/delta MAP). Femoral artery resistance remained below control levels. Lesions prolonged the time for 50% MAP recovery after nitroprusside by 93%. During phenylephrine-induced MAP increases, bilateral rFN lesions augmented reflex delta HR/delta MAP by 68%. In intact cats, the reflex decrease in HR after phenylephrine was blocked by electrical stimulation of the rFN, but appeared immediately after stimulation was stopped. Stimulation alone increased both MAP and HR. Propranolol failed to block either the increased HR or the suppression of reflex cardiodeceleration induced by rFN stimulation. Decreases in resting HR after rFN lesions may reflect removal of tonic cerebellar inhibition of cardiac parasympathetic tone. Thus, the cerebellum can influence autonomic output and modify baroreflex sensitivity by augmenting cardiovascular responses mediated by the sympathetic nervous system and inhibiting those mediated by the parasympathetic nervous system.

An observed pressor effect of the cerebellum during endotoxin shock in the dog.

The current study investigates the possibility that the cerebellum may be involved in the regulation of mean arterial pressure (MAP) during endotoxin shock in the anesthetized dog. The effect of intravenously injected Escherichia coli endotoxin on MAP in the cerebellectomized dog was compared to that observed in the intact animal. Even though removal of the cerebellum did not significantly affect MAP in a control group, the cerebellectomized animal (unlike the intact animal) was unable to recover from the initial hypotension typically seen immediately following an intravenous endotoxin injection. Previous investigators have demonstrated that stimulation of fastigial nuclei in the cerebellum increases MAP via beta-adrenergic activation of the renin-angiotensin system. Captopril (SQ 14,225, an angiotensin I-converting enzyme inhibitor) was used to determine whether this system could be responsible for the maintenance of MAP during endotoxin shock. When continuously infused into the intact dog given endotoxin, captopril suppressed MAP to a level similar to that of the cerebellectomized group. A similar response pattern to endotoxin was also observed in animals with a spinal transection at C2.

Effect of cerebral extracellular fluid acidity on total and regional cerebral blood flow.

Total and regional cerebral blood flow (CBF), and cerebrospinal fluid (CSF), and arterial blood acid-base status were measured in 26 chloralose-urethan-anesthetized dogs before and after 30 and 60 min of ventriculocisternal perfusion with artificial CSF equilibrated with 7% CO2 and containing either low (8.7 or 9.1 meq/l), normal (19.6 meq/l), or high (34.7 meq/l) bicarbonate ion concentration ([HCO3-]). An inverse linear relationship was observed between the CSF pH and total CBF. Regional blood flow changes were greater in structures that were closest to the ventricular system. In addition, regional blood flow changes were greater in all tissues studied after 60 min of perfusion than after 30. Perfusion with the control [HCO3-] caused no significant changes in either acid-base status or CBF. We believe that the regional cerebral blood flow changes are the result of changes in the H+ concentration gradient across the cerebral extracellular fluid (ECF) space due to the diffusional exchange of HCO3- between CSF and ECF. It is concluded that cerebral ECF acidity is important in the local regulation of cerebral blood flow.