Small Changes In Heart Rate Research Articles

Deficiency of CXXC finger protein 1 leads to small changes in heart rate but moderate epigenetic alterations and significant protein downregulation of hyperpolarization-activated cyclic nucleotide-gated 4 (HCN4) ion channels in mice.

The normal cardiac rhythm is generated in the sinoatrial node (SAN). Changes in ionic currents of the SAN may cause sinus arrhythmia. CXXC finger protein 1 (Cfp1) is an epigenetic regulator that is involved in transcriptional regulation of multiple genes. The purpose of this study was to explore whether Cfp1 controls SAN function through regulation of ion channel-related genes. Electrophysiological study, patch clamp recording, reverse transcriptase polymerase chain reaction, optical mapping, chromatin immunoprecipitation, and immunofluorescence staining were performed to evaluate the function of SAN and underlying mechanism on Cfp1 heterozygous knockout (Cfp1+/-) mice. Heart rate was slower slightly and SAN recovery time was longer in Cfp1+/- mice than controls. Whole-cell patch-clamp recording showed that the firing rate of action potentials was reduced in Cfp1+/- mice. The density of If current was reduced by 66% in SAN cells of Cfp1+/- mice but the densities of ICa, ICa-L, and ICa-T were not changed. The hyperpolarization-activated cyclic nucleotide-gated 4 (HCN4) mRNA level in SAN tissue of Cfp1+/- mice was reduced. The HCN4 protein was significantly decreased in SAN cells and tissues after heterozygous deletion of Cfp1. Chromatin immunoprecipitation assay on cultured HL-1 cells demonstrated that Cfp1 was enriched in the promoter regions of HCN4. Knockdown of Cfp1 reduced H3K4 trimethylation, H3K9 acetylation, and H3K27 acetylation of HCN4 promoter region. Deficiency of Cfp1 leads to small changes in heart rate by moderate epigenetic modification alterations and significant protein downregulation of HCN4 ion channels in mice.

Heart Rate Dependency of Large Artery Stiffness.

Carotid-femoral pulse wave velocity (cfPWV) quantifies large artery stiffness, it is used in hemodynamic research and is considered a useful cardiovascular clinical marker. cfPWV is blood pressure (BP) dependent. Intrinsic heart rate (HR) dependency of cfPWV is unknown because increasing HR is commonly accompanied by increasing BP. This study aims to quantify cfPWV dependency on acute, sympathovagal-independent changes in HR, independent of BP. Individuals (n=52, age 40-93 years, 11 female) with in situ cardiac pacemakers or cardioverter defibrillators were paced at 60, 70, 80, 90, and 100 bpm. BP and cfPWV were measured at each HR. Both cfPWV (mean [95% CI], 0.31 [0.26-0.37] m/s per 10 bpm; P<0.001) and central aortic diastolic pressure (3.78 [3.40-4.17] mm Hg/10 bpm; P<0.001) increased with HR. The HR effect on cfPWV was isolated by correcting the BP effects by 3 different methods: (1) statistically, by a linear mixed model; (2) mathematically, using an exponential relationship between BP and cross-sectional lumen area; and (3) using measured BP dependency of cfPWV derived from changes in BP induced by orthostatic changes (seated and supine) in a subset of subjects (n=17). The BP-independent effects of HR on cfPWV were quantified as 0.20 [0.11-0.28] m/s per 10 bpm (P<0.001, method 1), 0.16 [0.11-0.22] m/s per 10 bpm (P<0.001, method 2), and 0.16 [0.11-0.21] m/s per 10 bpm (P<0.001, method 3). With a mean HR dependency in the range of 0.16 to 0.20 m/s per 10 bpm, cfPWV may be considered to have minimal physiologically relevant changes for small changes in HR, but larger differences in HR must be considered as contributing to significant differences in cfPWV.

Response to Fluid Boluses in the Fluid and Catheter Treatment Trial

Recent emphasis has been placed on methods to predict fluid responsiveness, but the usefulness of using fluid boluses to increase cardiac index in critically ill patients with ineffective circulation or oliguria remains unclear. This retrospective analysis investigated hemodynamic responses of critically ill patients in the ARDS Network Fluid and Catheter Treatment Trial (FACTT) who were given protocol-based fluid boluses. Fluid responsiveness was defined as ≥ 15% increase in cardiac index after a 15 mL/kg fluid bolus. A convenience sample of 127 critically ill patients enrolled in FACTT was analyzed for physiologic responses to 569 protocolized crystalloid or albumin boluses given for shock, low urine output (UOP), or low pulmonary artery occlusion pressure (PAOP). There were significant increases in mean central venous pressure (9.9 ± 4.5 to 11.1 ± 4.8 mm Hg, P < .0001) and mean PAOP (11.6 ± 3.6 to 13.3 ± 4.3 mm Hg, P < .0001) following fluid boluses. However, there were no significant changes in UOP, and there were clinically small changes in heart rate, mean arterial pressure, and cardiac index. Only 23% of fluid boluses led to a ≥ 15% change in cardiac index. There was no significant difference in the frequency of fluid responsiveness between boluses given for shock or oliguria vs boluses given only for low PAOP (24.0% vs 21.8%, P = .59). There were no significant differences in 90-day survival, need for hemodialysis, or return to unassisted breathing between patients defined as fluid responders and fluid nonresponders. In this cohort of critically ill patients with ARDS who were previously resuscitated, the rate of fluid responsiveness was low, and fluid boluses only led to small hemodynamic changes.

Electrocardiographic Studies of Romidepsin Demonstrate Its Safety and Identify a Potential Role for KATP Channel

Romidepsin is a histone deacetylase inhibitor (HDI) approved for the treatment of both cutaneous and peripheral T-cell lymphoma (CTCL and PTCL). During development, a thorough assessment of cardiac toxicity was conducted. A phase II single-agent nonrandomized study of romidepsin was conducted in patients with CTCL or PTCL who had progressed after at least 1 prior systemic therapy. Results for the first 42 patients enrolled on the NCI 1312 phase II study of romidepsin in CTCL or PTCL showed no cardiac toxicity based on serial electrocardiograms (ECG), troponins, and MUGA scans/echocardiograms. The cardiac assessments reported herein confirm the safety of romidepsin among 131 enrolled patients, while supporting a role for electrolyte replacement. Heart rate increased an average 11 bpm following romidepsin infusion; there was no evidence of increased arrhythmia. Criteria for potassium/magnesium replacement were met before 55% of 1365 romidepsin doses; an association with hypoalbuminemia was confirmed. We propose a mechanism for ST segment flattening and depression, the most common ECG abnormalities observed: HDI-induced alteration of the activity or expression of KATP channels. In addition, examination of the variants of the active transporter of romidepsin, ABCB1, showed a trend toward smaller heart rate changes in the peri-infusion period among wild-type than variant diplotypes. We conclude that in the context of appropriate attention to electrolyte levels, the data support the cardiac safety of romidepsin.

Long-acting dihydropyridine calcium-channel blockers and sympathetic nervous system activity in hypertension: A literature review comparing amlodipine and nifedipine GITS

Calcium-channel blockers (CCBs) constitute a diverse group of compounds but are often referred to as a single homogeneous class of drug and the clinical responses indiscriminately summarized. Even within the dihydropyridine subgroup, there are significant differences in formulations, pharmacokinetics, durations of action and their effects on blood pressure, heart rate, end organs and the sympathetic nervous system. Amlodipine and nifedipine in the gastrointestinal therapeutic system (GITS) formulation are the most studied of the once-daily CCBs. Amlodipine has an inherently long pharmacokinetic half-life, whereas, in contrast, nifedipine has an inherently short half-life but in the GITS formulation the sophisticated delivery system allows for once-daily dosing. This article is derived from a systematic review of the published literature in hypertensive patients. The following search terms in three main databases (MEDLINE, Embase, Science Citation Index) from 1990 to 2011 were utilized: amlodipine, nifedipine, sympathetic nervous system, sympathetic response, sympathetic nerve activity, noradrenaline, norepinephrine and heart rate. More than 1500 articles were then screened to derive the relevant analysis. As markers of sympathetic nervous system activation, studies of plasma norepinephrine concentrations, power spectral analysis, muscle sympathetic nerve activity and norepinephrine spillover were reviewed. Overall, each drug lowered blood pressure in hypertensive patients in association with only small changes in heart rate (i.e. <1 beat/min). Plasma norepinephrine concentrations, as the most widely reported marker of sympathetic nervous system activity, showed greater increases in patients treated with amlodipine than with nifedipine GITS. The evidence indicates that both these once-daily dihydropyridine CCBs lower blood pressure effectively with minimal effects on heart rate. There are small differences between the drugs in the extent to which each activates the sympathetic nervous system with an overall non-significant trend in favour of nifedipine GITS.

C-001 EFFECTS OF LONG ACTING DIHYDROPYRIDINE CALCIUM CHANNEL BLOCKERS ON SYMPATHETIC ACTIVITY IN HYPERTENSION

Background Calcium channel blockers (CCBs) constitute a diverse group of compounds, with three principal subgroups and multiple variations in formulation. CCBs are often referred to as a single homogeneous class of drug and the clinical responses indiscriminately summarized. Even within the main subgroup, the dihydropyridine subgroup, there are significant differences in formulations, pharmacokinetics, durations of action and their effects on blood pressure, heart rate, end organs and the sympathetic nervous system. Amlodipine and Nifedipine in the GITS formulation are the most studied of the once daily CCBs and are registered in most major countries worldwide. Amlodipine has an inherently long pharmacokinetic half life whereas, in contrast, nifedipine has an inherently short half life but in the GITS formulation the sophisticated delivery system allows for once daily dosing. Methods This presentation is derived from a systematic review of the published literature in hypertensive patients to date. The following search terms in three main databases (MEDLINE, Embase, Science Citation Index) from 1990 to 2011 were utilized: amlodipine, nifedipine, sympathetic nervous system, sympathetic response, sympathetic nerve activity, noradrenaline, norepinephrine and heart rate. More than 1,500 articles were then screened to derive the relevant analysis. Results As markers of sympathetic nervous system activation, plasma norepinephrine, power spectral analysis, muscle sympathetic nerve activity and norepinephrine spillover studies were reviewed. Although direct comparisons of the two drugs in one study would present the ideal this was rarely reported. Durations of treatment with either drug ranged from 1 week to 52 weeks. Doses of amlodipine ranged from 2.5 to 10 mg once a day and 20 to 150 mg once a day for nifedipine GITS. Each drug lowered blood pressure in patients with small changes in heart rate (i.e. < 1 b/min). Plasma norepinephrine measurements were the most reported marker of sympathetic nervous system activity and showed a greater increase in patients treated with amlodipine than nifedipine GITS. Conclusions The evidence indicates that both these once daily dihydropyridine CCBs lower blood pressure effectively with minimal effects on heart rate. However, there are small differences between the drugs in the extent to which each activates the sympathetic nervous system: overall, the available evidence favours nifedipine GITS.

Timing on 16-Slice Scanner and Implications for 64-Slice Cardiac CT: Do You Start Scanning Immediately After Breath Hold?

Slow heart rate and small changes in heart rate are factors for improving image quality on spiral cardiac computed tomography (CT). The purpose of this study is to investigate whether it is possible to improve non-enhanced cardiac CT quality by delaying the data-acquisition window after breath hold. Electrocardiograph files (n = 240) for 16-slice non-enhanced cardiac CT scans were analyzed. Mean heart rates and maximal changes in heart rates between adjacent cardiac cycles were compared between phase 1 (defined as cardiac cycles 1-5), phase 2 (cardiac cycles 2-6), ... , and phase 6 (cardiac cycles 6-10). Heart rates gradually increased by phases, but were limited to a range of 66.8-68.0 beats/min. Maximal changes in heart rates were 2.5 beats/min (phase 1) at the highest and 1.3 beats/min (phases 5 and 6) at the lowest (t-test; P < .01). Maximal changes in heart rates for more than five beats/min occurred in 24, eight, and eight patients on phases 1, 5, and 6, respectively (chi-square test; P < .01). The delayed scan (four or five cardiac cycles after breath hold) has the potential to improve the quality of non-enhanced cardiac CT.

610 The evoked cardiac response as a function of cognitive load in subjects differing on the performance of the divided attention task (DIVA)

We report research on different phasic evoked cardiac responses associated with differences in personality. Heart rate changes were examined in relation to the stable individual difference variables of psychoticism, neuroticism and extraversion. Subjects were divided into different pairs of subgroups on the basis of the measure of their personality dimension scores (above and below the group median). Each subject received 10 innocuous auditory stimuli with randomly varying interstimulus intervals. Stimuli were presented in one of two conditions. In the irrelevant condition there was no task, while in the relevant condition, subjects were required to count the number of stimuli presented. A main effect of condition was obtained in the evoked cardiac response. The initial heart rate deceleration was significantly larger in the irrelevant condition and a later acceleration was significantly larger in the relevant condition. High psychoticism subjects had smaller heart rate changes to the irrelevant stimuli and smaller differences between the relevant and irrelevant conditions than did low psychoticism subjects. High neuroticism subjects, compared with low neuroticism subjects, showed some enhanced cardiac responding to relevant stimuli, but there were no effects of differences in extraversion. The data are discussed in terms of the intensity of stimulus processing (both physical and cognitive) as a factor that may be related fundamentally to stable individual differences in personality.

The evoked cardiac response as a function of cognitive load differs between subjects separated on the main personality dimensions

We report research on different phasic evoked cardiac responses associated with differences in personality. Heart rate changes were examined in relation to the stable individual difference variables of psychoticism, neuroticism and extraversion. Subjects were divided into different pairs of subgroups on the basis of the measure of their personality dimension scores (above and below the group median). Each subject received 10 innocuous auditory stimuli with randomly varying interstimulus intervals. Stimuli were presented in one of two conditions. In the irrelevant condition there was no task, while in the relevant condition, subjects were required to count the number of stimuli presented. A main effect of condition was obtained in the evoked cardiac response. The initial heart rate deceleration was significantly larger in the irrelevant condition and a later acceleration was significantly larger in the relevant condition. High psychoticism subjects had smaller heart rate changes to the irrelevant stimuli and smaller differences between the relevant and irrelevant conditions than did low psychoticism subjects. High neuroticism subjects, compared with low neuroticism subjects, showed some enhanced cardiac responding to relevant stimuli, but there were no effects of differences in extraversion. The data are discussed in terms of the intensity of stimulus processing (both physical and cognitive) as a factor that may be related fundamentally to stable individual differences in personality.

Effects of high-frequency ventilation and PEEP on carotid baroreceptor reflexes.

We tested the hypothesis that altering the pattern and/or magnitude of discharge of pulmonary stretch receptors (PSRs) would alter baroreceptor reflexes in anesthetized aortic-denervated cats. Carotid baroreceptor control of mean arterial pressure (MAP), heart rate (HR), and hindlimb perfusion pressure (PPhl) was examined by changing carotid sinus pressure (CSP) from 50 to 225 mmHg. The pattern of PSR discharge was changed by switching conventional mechanical ventilation (CMV) to high-frequency ventilation (HFV). Magnitude of PSR discharge was altered by changing positive end-expiratory pressure (PEEP). Altering the discharge pattern of PSR had no effect on CSP-MAP or CSP-PPhl relationships; small changes in HR were observed. Increasing PSR activity by increasing PEEP during CMV (from 3 to 9 cmH2O) depressed CSP-MAP relationship, set point, and threshold pressure. However, the depression in CSP-MAP relationship and set point during PEEP was unrelated to PSR activation, because these changes were not abolished after bilateral vagotomy. CSP-PPhl relationship was significantly elevated during PEEP before and after vagotomy, suggesting activation of a nonvagally mediated vasoconstrictory mechanism instead of PSR-mediated depressor reflex. CSP-HR relationship during PEEP showed a slight elevation, which was abolished after vagotomy. We conclude that despite minor increases in HR, altering the pattern of magnitude of PSR activity with HFV and PEEP has no significant effect on carotid baroreceptor regulation of systemic circulation. Hemodynamic changes observed during PEEP were likely due to its mechanical effect on cardiac output and activation of other cardiopulmonary receptors rather than to the increase in PSR activity.

Atropine-neostigmine mixture

To the Editor: The recent study of Naguib and Mohammed 1 leaves me dissatisfied. These investigators studied the doses of atropine required to prevent neostigmine (0.04-0.06 mg.kg -t) from lowering the heart rate below baseline (pre.reversal) in 50 and 95 per cent of patients after antagonism of nondepolarizing neuromuscular blockade with neostigmine-atropine mixtures. They estimated that .the EDso and EDgs values for atropine were approximately 0.035 and 0.055 kg -I respectively. They conclude that appropriate doses of atropine when used with neostigmine should be greater than that used. First, I am not sure that the authors have asked the right question. Is any decrease in heart rate from control really of clinical significance or a valid definition of bradycardia? For example, in group A-I the decrease in mean heart rate from a baseline of 92 to a low of 70 per minute may be statistically significant and real, but is it important? Of far greater interest is the actual number or percentage of patients who manifested heart rates of less than 60 or at least some fixed standard. In addition, in constructing their dose-response relationships the authors have not differentiated between large and small changes in heart rate. A decrease from 90 to 60.min -1 was given the same weight as a decrease from 80 to 70. This is simply not a sensible approach. Second, if commonly used dosages are not appropriate, what practical recommendations do the authors make? Do they suggest that doses of atropine of 0.05 to 0.06 mg. kg -1 should be employed clinically? This is the implied message of the paper and I think a potentially dangerous one. The central nervous system effects of 4 mg of atropine in a 70 kg adult deserve to be mentioned. If the authors really believe that prevention of any decrease in heart rate is a desirable goal and that these doses of atropine are warranted, then the virtues of glycopyrrolate vs atropine must also be discussed.

口腔手術術中の各種ストレスに対する生理学的反応の計測 循環器疾患患者について

1. Physiological responses during tooth extraction, including plethysmogram, GSR, heart rate, blood pressure and RPP, were measured, and the obtained data were recorded and analyzed by computer. As the subjects, 127 healthy adults, 67 patients with hypertension and 41 patients with heart disease were used.2. When the amounts of stress were compared according to the treatments used, plethysmogram and GSR were found to be larger at the time of anesthesia and tooth extraction and during a preoperative period; heart rates increased after anesthesia; changes in blood pressure were larger at the time of anesthesia and tooth extraction.3. When the amounts of stress were compared according to the subjects' ages, responses with plethysmograph were large in the age group of 39 years or below, but were small in the age group of 60 years or above. Similar results were seen with GSR. Heart rates were fewer in aged patients than in younger patients, and the aged patients also showed smaller heart rate changes. Blood pressure was the highest and showed the greatest changes in the age group of 40-50 years.4. In comparison of the diseased group with the healthy group, plethysmograms had larger waves in the diseased group, and this group showed poor responses. Changes in heart rates were larger in the diseased group at the time of tooth extraction. The diseased group showed greater changes in blood pressure during a preoperative period and at the time of anesthesia and tooth extraction than did the healthy group. RPP was larger in the deseased group than in the healthy group, and changes in RPP were higher at the time of anesthesia and tooth extraction.5. Plethysmogram and GSR well reflected mental responses, while the other parameters well reflected cardiovascular dynamics.

Transmitral velocities measured by pulsed Doppler in healthy volunteers: effects of acute changes in blood pressure and heart rate.

The effect of a two minute cold pressor test on transmitral velocities measured by pulsed Doppler was studied in 11 healthy volunteers. Blood pressure increased significantly during cold immersion but peak atrial and peak early diastolic transmitral velocities and their ratio (A:E) were unchanged. There was no correlation between changes in Doppler variables and changes in calculated mean arterial blood pressure during the test. Heart rate changes were variable and not related to changes in blood pressure. In individual people the change in pulse interval during cold immersion was significantly and inversely correlated with the change in the A:E ratio. The large acute increase in arterial pressure seen during the cold pressor test in normal volunteers had no consistent effect on the transmitral velocity profile although small changes in heart rate were associated with large changes in A:E ratio. The effect of small changes in heart rate may be of considerable importance in determining transmitral velocity profiles. Thus in clinical and experimental studies in which the heart rate is not controlled, Doppler data on transmitral flow should be interpreted with caution.

Cardiovascular Properties of MS-857, a New and Potent Cardiotonic Agent, on Normal and Failing Hearts

The cardiovascular properties of MS-857 [4-acetyl-1-methyl-7-(4-pyridyl)-5,6,7,8-tetrahydro-3(2H)-isoquinolinone ], a novel cardiotonic agent, were investigated in anesthetized and conscious dogs. MS-857 (1-100 micrograms/kg i.v.) produced a significant and dose-dependent increase in cardiac contractility with relatively small changes in heart rate and blood pressure. This indicates a sizable separation between positive inotropic and other effects of MS-857. Oral administration of MS-857 to conscious dogs (0.1-1 mg/kg) also produced a sustained increase in cardiac contractility in a dose-dependent manner. The total duration of action was longer than 7 h at a dose of 1 mg/kg p.o. There occurred no arrhythmias and no changes in animal behavior. After chronic oral administration, MS-857 completely retained its activities, indicating the lack of tachyphylaxis. In the acute heart failure models induced by either propranolol or pentobarbital, MS-857 reversed the cardiac depressant effects of these drugs. Moreover, MS-857 also significantly improved the pentobarbital-induced heart failure in the heart-lung preparation. MS-857 did not inhibit the Na+, K+-ATPase, but inhibited the phosphodiesterase (PDE) III selectively, both of which were prepared from the dog ventricular muscle. Thus, MS-857 can be characterized as a potent nonsympathomimetic, nonglycoside cardiotonic drug with a selective inhibitory activity on PDE III. The cardiovascular properties revealed by this study strongly suggest that MS-857 will exert a beneficial effect in the treatment of congestive heart failure.

Assessment of the cardiac effects of hemodialysis with systolic time intervals and echocardiography

The acute effects of hemodialysis on left ventricular (LV) function were studied with the use of externally recorded LV systolic time intervals and echocardiography; 10 patients with normal or near-normal predialysis LV function and no circulatory congestion were studied. Hemodialysis significantly decreased the LV ejection time (LVET) from 270 +/- 9 ms to 237 +/- 10 ms (p less than 0.001); no significant change was noted in the preejection period (PEP). The PEP/LVET ratio increased from 0.41 +/- 0.05 to 0.45 +/- 0.06 (p less than 0.05). The LV end-diastolic dimension decreased from 5.3 +/- 0.3 cm to 4.8 +/- 0.3 cm (p less than 0.001). Fractional shortening and ejection fraction did not change significantly, but hemodialysis slightly increased mean VCF from 1.2 +/- 0.1 s-1 to 1.4 +/- 0.1s-1 (p less than 0.005). Hemodialysis was associated with a 17% decrease (87 +/- 8 ml to 72 +/- 7 ml; p less than 0.001) in LV stroke volume as calculated from echocardiographic data. Small changes in heart rate and blood pressure were insignificant. We conclude that the postdialysis reduction in stroke volume was due primarily to an acute decrease in LV preload; dialysis also appears to be associated with a small increase in the LV contractile state.

Lateral hypothalamic lesions: Effects on pavlovian cardiac and eyeblink conditioning in the rabbit

Rabbits received either bilateral lesions of the far lateral hypothalamus (LH), or sham-operate lesions. After recovery from surgery the animals were exposed to Pavlovian conditioning in which eyeblink (EB), electromyographic (EMG), and heart rate (HR) conditioned responses (CRs) were recorded. Adaptation, acquisition and extinction training were studied. Subsequent to conditioning, free-field activity, paraorbital electric shock thresholds, and HR unconditioned responses (URs) were measured. At the end of behavioral testing forebrain norepinephrine (NE), dopamine (DA), an serotonin (5-HT) concentrations were assessed. Animals with LH lesions did not differ from controls on EB responding during either adaptation or acquisition. However, lesioned animals revealed more EB CRs during extinction than control animals. EMG CRs were minimal in both groups of animals. Lesioned animals showed smaller HR changes than control animals during all phases of training, although HR CRs tended to consist of bradycardia in all animals. No differences were observed in either shock thresholds or open field activity as a result of LH lesions. Cortical and hippocampal 5-HT and NE concentrations were significantly depleted in lesioned as compared to control animals. These findings were interpreted within the framework of the phasic control of attention by midbrain modulation of forebrain structures; however, the interruption of downward going fibers which mediate brain stem cardiac control cannot be ruled out.

Cardiotonic activity of amrinone--Win 40680 [5-amino-3,4'-bipyridine-6(1H)-one

The cardiotonic activity of a new, noncatechol, nonglycoside agent, amrinone, was investigated in vitro and in anesthestized and unanesthetized dogs. Amrinone (3-100 microgram/ml) caused a dose-dependent increase in papillary muscle developed tension and df/dt without significant changes in duration of the contractile cycle or time-to-peak tension. Amrinone induced slight increases in right atrial rate with no changes in electrophysiological properties of the cat papillary muscle or dog Purkinje fibers. In anesthetized dogs, intravenous bolus injections of amrinone at doses ranging from 1 to 10 mg/kg caused increases in cardiac contractile force and left ventricular dp/dt max with relatively small changes in heart rate and blood pressure. No significant changes in lead II ECG were observed. In unanesthetized dogs, intravenous infusion of amrinone (10-100 microgram/kg per min) caused increases in left ventricular dp/dt max and only small changes in heart rate and blood pressure. Amrinone, tested orally in this model at doses of 2-10 mg/kg, produced a positive inotropic effect with a rapid onset and long duration of action. The inotropic response to amrinone was not blocked by propranolol, dibenzyline, chlorisondamine, atropine, metiamide, or reserpine. Amrinone's inotropic response was not associated with significant alterations in cardiac norepinephrine, phosphodiesterase, cyclic AMP, or Na+, K+-activated ATPase.

HAEMODYNAMIC EFFECTS OF DOPAMINE AND DOPAMINE COMBINED WITH NITROGLYCERIN IN PATIENTS SUBJECTED TO CORONARY BYPASS SURGERY

The haemodynamic effects of dopamine and dopamine with nitroglycerin were evaluated in eight patients with coronary heart disease who underwent aortocoronary bypass surgery. The study was performed under anaesthesia and before surgery. Dopamine 8 micrograms kg-1 min-1 alone produced a marked increase of the cardiac index from 2.47 to 3.47 litre min-1 m-2 but only small changes in heart rate (from 65 to 68 beat min-1). This improvement in cardiac performance was accompanied by an increase of the mean pulmonary artery pressure from 10.9 to 21.3 mm Hg and in the left ventricular filling pressure from 6.1 to 13.8 mm Hg with unchanged systemic and pulmonary vascular resistance. Mean arterial pressure increased from 72 to 103 mm Hg. Simultaneous infusion of dopamine (8 micrograms kg-1 min-1) and nitroglycerin (mean dose 0.5 microgram 21.3 to 14.4 mm Hg) and of left ventricular filling pressure (from 13.8 to 7.9 mm Hg). Cardiac index (from 3.47 to 3.34 litre min-1 m-2) and mean arterial pressure (from 103 to 95 mm Hg) were not reduced to the same extent by the addition of nitroglycerin. The combined treatment of dopamine with nitroglycerine seems to be of value in patients with pre-existing high left ventricular filling pressure or with pulmonary hypertension.

Autonomic correlates of depression and clinical improvement following electroconvulsive shock therapy.

ABSTRACTElectrodermal responses (EDRs) and heart rate (HR) were recorded during a variety of tasks from 20 hospitalized depressed patients before and after a series of electroconvulsive shock treatments (ECTs). The depressed patients, compared to nondepressed controls during the pre‐ECT test, exhibited lower skin conductance levels, smaller phasic skin conductance responses with longer latencies, higher tonic HR, and smaller HR changes to stimuli. This response pattern suggests a complex state of “environmental rejection” coupled with “low arousal” in the depressed patients. Certain EDR measures were related to the severity of depressive symptomatology while tonic HR was related to the agitation/retardation symptoms. Patients who subsequently responded well following ECT were more like the controls on certain pre‐treatment measures than those who failed to respond favorably. There were little EDR or HR changes following ECT and what changes did occur were unrelated to differences in clinical improvement. It was suggested that, despite temporary clinical improvement following ECT, depressed patients have a chronic affective disorder which is reflected in the EDR and HR measures.

Human cardiovascular and respiratory responses to graded muscle ischemia.

Responses of heart rate (HR), mean arterial blood pressure (MAP) ventilation (VE), and forearm blood flow (FBF) to different degrees of leg muscle ischemia were measured in eight subjects in a four-part experiment. Part I. Total circulatory occlusion (OCCL) of resting legs for 15 min had little or no effect on HR, MAP, VE, or FBF. Part II. OCCL of the legs for 3 min immediately after exercise at 50-250 W did not affect HR or end-tidal CO2; it lowered VO2 and VE and prevented recovery of MAP. Part III. OCCL beginning at end and 10, 20, 30 s before end of 7-min exercise (100-150 W) and continuing 3 min into recovery period produced sustained and graded increments (5-10 mmHg) in MAP, only small changes in HR, and accelerated recovery of VE while end-tidal CO2 remained constant. Part IV. OCCL at end and 30 s before end of exercise increased FBF 2.5-3.5 times; both skin and muscle vasodilated. Thus muscle ischemia preceded by exercise can raise MAP without affecting VE, whereas baroreflexes may lower HR and raise FBF. The results suggest the presence of muscle chemoreceptors whose major effect is on MAP.