Comparison of clinical outcomes between transthoracic echocardiography- and X-ray-guided left bundle branch pacing for bradycardia: A randomized controlled trial.

INTRODUCTION: Left bundle branch pacing (LBBP) is a physiological pacing modality. However, the long procedure and fluoroscopy time of LBBP is still a problem. This study aims to compare the clinical outcomes between transthoracic echocardiography (TTE)- and X-ray-guided LBBP. METHODS: This is a single-center, prospective, randomized controlled study. Consecutive patients who underwent LBBP in our team from June 2022 to November 2022 were enrolled. Procedure and fluoroscopy time, pacing parameters, electrophysiological and echocardiographic characteristics, as well as complications were recorded at implantation and during follow-up. RESULTS: In this study, 60 patients were enrolled and divided into two groups: 30 patients were allocated to the X-ray group and the remaining 30 to the TTE group. There was no significant difference in the success rate between the two groups (86.7% vs. 76.7%, p = .317). The procedure time of TTE group was comparable to that of the X-ray group (9.0 vs. 12.0 min, p = .063). However, the fluoroscopy time in the TTE group was significantly lower than that of the X-ray group (2.5 vs. 5.0 min, p = .002). There were no statistically significant differences in pacing parameters, electrophysiological and echocardiographic characteristics, or complications between the two groups at implantation and during follow-up. CONCLUSION: TTE-guided LBBP is a feasible and safe method. Compared with X-ray, TTE showed a comparable success rate and procedure time, but it could significantly reduce the fluoroscopy time of LBBP.

Vagal sensory neurons mediate the Bezold-Jarisch reflex and induce syncope.

Visceral sensory pathways mediate homeostatic reflexes, the dysfunction of which leads to many neurological disorders1. The Bezold-Jarisch reflex (BJR), first described2,3 in 1867, is a cardioinhibitory reflex that is speculated to be mediated by vagal sensory neurons (VSNs) that also triggers syncope. However, the molecular identity, anatomical organization, physiological characteristics and behavioural influence of cardiac VSNs remain mostly unknown. Here we leveraged single-cell RNA-sequencing data and HYBRiD tissue clearing4 to show that VSNs that express neuropeptide Y receptor Y2 (NPY2R) predominately connect the heart ventricular wall to the area postrema. Optogenetic activation of NPY2R VSNs elicits the classic triad of BJR responses-hypotension, bradycardia and suppressed respiration-and causes an animal to faint. Photostimulation during high-resolution echocardiography and laser Doppler flowmetry with behavioural observation revealed a range of phenotypes reflected in clinical syncope, including reduced cardiac output, cerebral hypoperfusion, pupil dilation and eye-roll. Large-scale Neuropixels brain recordings and machine-learning-based modelling showed that this manipulation causes the suppression of activity across a large distributed neuronal population that is not explained by changes in spontaneous behavioural movements. Additionally, bidirectional manipulation of the periventricular zone had a push-pull effect, with inhibition leading to longer syncope periods and activation inducing arousal. Finally, ablating NPY2R VSNs specifically abolished the BJR. Combined, these results demonstrate a genetically defined cardiac reflex that recapitulates characteristics of human syncope at physiological, behavioural and neural network levels.

Clinical outcomes of left bundle branch area pacing compared to right ventricular pacing: Results from the Geisinger-Rush Conduction System Pacing Registry.

BACKGROUND: Left bundle branch area pacing (LBBAP) has been shown to be a feasible option for patients requiring ventricular pacing. OBJECTIVE: The purpose of this study was to compare clinical outcomes between LBBAP and RVP among patients undergoing pacemaker implantation METHODS: This observational registry included patients who underwent pacemaker implantations with LBBAP or RVP for bradycardia indications between April 2018 and October 2020. The primary composite outcome included all-cause mortality, heart failure hospitalization (HFH), or upgrade to biventricular pacing. Secondary outcomes included the composite endpoint among patients with a prespecified burden of ventricular pacing and individual outcomes. RESULTS: A total of 703 patients met inclusion criteria (321 LBBAP and 382 RVP). QRS duration during LBBAP was similar to baseline (121 ± 23 ms vs 117 ± 30 ms; P = .302) and was narrower compared to RVP (121 ± 23 ms vs 156 ± 27 ms; P <.001). The primary composite outcome was significantly lower with LBBAP (10.0%) compared to RVP (23.3%) (hazard ratio [HR] 0.46; 95%T confidence interval [CI] 0.306-0.695; P <.001). Among patients with ventricular pacing burden >20%, LBBAP was associated with significant reduction in the primary outcome compared to RVP (8.4% vs 26.1%; HR 0.32; 95% CI 0.187-0.540; P <.001). LBBAP was also associated with significant reduction in mortality (7.8% vs 15%; HR 0.59; P = .03) and HFH (3.7% vs 10.5%; HR 0.38; P = .004). CONCLUSION: LBBAP resulted in improved clinical outcomes compared to RVP. Higher burden of ventricular pacing (>20%) was the primary driver of these outcome differences.

Indole-3-propionic acid, a tryptophan-derived bacterial metabolite, increases blood pressure via cardiac and vascular mechanisms in rats.

Recent evidence suggests that gut bacteria-derived metabolites interact with the cardiovascular system and alter blood pressure (BP) in mammals. Here, we evaluated the effect of indole-3-propionic acid (IPA), a gut bacteria-derived metabolite of tryptophan, on the circulatory system. Arterial BP, electrocardiographic, and echocardiographic (ECHO) parameters were recorded in male, anesthetized, 12-wk-old Wistar-Kyoto rats at baseline and after intravenous administration of either IPA or vehicle. In additional experiments, rats were pretreated with prazosin or pentolinium to evaluate the involvement of the autonomic nervous system in cardiovascular responses to IPA. IPA's concentrations were measured using ultra-high performance liquid chromatography tandem mass spectrometry. The reactivity of endothelium-intact and -denuded mesenteric resistance arteries was tested. Cells' viability and lactate dehydrogenase (LDH) cytotoxicity assays were performed on cultured cardiomyocytes. IPA increased BP with a concomitant bradycardic response but no significant change in QTc interval. The pretreatment with prazosin and pentolinium reduced the hypertensive response. ECHO showed increased contractility of the heart after the administration of IPA. Ex vivo, IPA constricted predilated and endothelium-denuded mesenteric resistance arteries and increased metabolic activity of cardiomyocytes. IPA increases BP via cardiac and vascular mechanisms in rats. Furthermore, IPA increases cardiac contractility and metabolic activity of cardiomyocytes. Our study suggests that IPA may act as a mediator between gut microbiota and the circulatory system.

The cardiovascular effects of amodiaquine and structurally related antimalarials: An individual patient data meta-analysis.

BACKGROUND: Amodiaquine is a 4-aminoquinoline antimalarial similar to chloroquine that is used extensively for the treatment and prevention of malaria. Data on the cardiovascular effects of amodiaquine are scarce, although transient effects on cardiac electrophysiology (electrocardiographic QT interval prolongation and sinus bradycardia) have been observed. We conducted an individual patient data meta-analysis to characterise the cardiovascular effects of amodiaquine and thereby support development of risk minimisation measures to improve the safety of this important antimalarial. METHODS AND FINDINGS: Studies of amodiaquine for the treatment or prevention of malaria were identified from a systematic review. Heart rates and QT intervals with study-specific heart rate correction (QTcS) were compared within studies and individual patient data pooled for multivariable linear mixed effects regression. The meta-analysis included 2,681 patients from 4 randomised controlled trials evaluating artemisinin-based combination therapies (ACTs) containing amodiaquine (n = 725), lumefantrine (n = 499), piperaquine (n = 716), and pyronaridine (n = 566), as well as monotherapy with chloroquine (n = 175) for uncomplicated malaria. Amodiaquine prolonged QTcS (mean = 16.9 ms, 95% CI: 15.0 to 18.8) less than chloroquine (21.9 ms, 18.3 to 25.6, p = 0.0069) and piperaquine (19.2 ms, 15.8 to 20.5, p = 0.0495), but more than lumefantrine (5.6 ms, 2.9 to 8.2, p < 0.001) and pyronaridine (-1.2 ms, -3.6 to +1.3, p < 0.001). In individuals aged ≥12 years, amodiaquine reduced heart rate (mean reduction = 15.2 beats per minute [bpm], 95% CI: 13.4 to 17.0) more than piperaquine (10.5 bpm, 7.7 to 13.3, p = 0.0013), lumefantrine (9.3 bpm, 6.4 to 12.2, p < 0.001), pyronaridine (6.6 bpm, 4.0 to 9.3, p < 0.001), and chloroquine (5.9 bpm, 3.2 to 8.5, p < 0.001) and was associated with a higher risk of potentially symptomatic sinus bradycardia (≤50 bpm) than lumefantrine (risk difference: 14.8%, 95% CI: 5.4 to 24.3, p = 0.0021) and chloroquine (risk difference: 8.0%, 95% CI: 4.0 to 12.0, p < 0.001). The effect of amodiaquine on the heart rate of children aged <12 years compared with other antimalarials was not clinically significant. Study limitations include the unavailability of individual patient-level adverse event data for most included participants, but no serious complications were documented. CONCLUSIONS: While caution is advised in the use of amodiaquine in patients aged ≥12 years with concomitant use of heart rate-reducing medications, serious cardiac conduction disorders, or risk factors for torsade de pointes, there have been no serious cardiovascular events reported after amodiaquine in widespread use over 7 decades. Amodiaquine and structurally related antimalarials in the World Health Organization (WHO)-recommended dose regimens alone or in ACTs are safe for the treatment and prevention of malaria.

Comparison of synchronization between left bundle branch and his bundle pacing in atrial fibrillation patients: An intra-patient-controlled study.

BACKGROUND: His bundle pacing (HBP) is a physiological pacing strategy to preserve the electrical synchrony of ventricular conduction and left ventricular (LV) function. Left bundle branch pacing (LBBP) has emerged as an alternative physiological pacing technique. OBJECTIVE: To evaluate cardiac electrical and mechanical synchrony comparing LBBP and HBP in patients with permanent atrial fibrillation (AF). METHODS: Consecutive patients with symptomatic bradycardia and AF were enrolled from January to June of 2019. The cardiac electrical and mechanical synchrony in different pacing mode were evaluated at baseline and after implantation. RESULTS: Both HBP and LBBP were performed in 20 patients. LBBP significantly widened the QRS duration compared with the intrinsic conduction (113.2 ± 14.5  vs. 96.5 ± 16.2 ms; p = .01), while HBP did not (104.5 ± 22.3  vs. 96.5 ± 16.2 ms; p = .12). Both LBBP and HBP patients had similar LV myocardial strain measurements for the mechanical synchrony evaluation without significant change compared with baseline. There was no significant difference in right ventricular synchrony measurement between LBBP and HBP. Compared to HBP, LBBP had less interventricular synchrony (IMVD, 14.7 ± 9.2  vs. 3.1 ± 12.7 ms, p < .01; Ts-LV-RV, 37.9 ± 10.7  vs. 18.5 ± 10.8 ms, p < .001). CONCLUSIONS: Although LBBP's a physiological pacing mode can achieve a similar cardiac electrical and mechanical synchronization when compared to HBP, LBBP results in modest delay in RV activation, and the clinical implication remains to be studied.

Cardiac response in aversive and appetitive olfactory conditioning: Evidence for a valence-independent CS-elicited bradycardia.

While the examination of conditioned cardiac responses is well established in human fear conditioning research, comparable studies using less-aversive or rather appetitive unconditioned stimuli (UCS) are sparse and results are mixed. Therefore, the aim of this study was a systematic analysis of cardiac reactions in aversive and appetitive conditioning. Olfactory stimuli were used as unconditioned stimuli as they are suitable reinforcers in both an aversive and an appetitive conditioning offering the opportunity for a comparison between conditioned responses. In total, n = 86 participants took part in both an aversive and an appetitive differential conditioning task with a counterbalanced order across participants. Aversive or appetitive odors, respectively, served as UCS and neutral geometrical figures as CS. Subjective ratings, skin conductance response (SCRs), and evoked cardiac reactions were analyzed and compared between tasks. Conditioned responses in subjective ratings could be observed in both aversive conditioning and appetitive conditioning, while SCRs discriminated between CS+ and CS- in aversive conditioning only. Regarding conditioned cardiac responses, the deceleration for the CS+ was longer than for the CS- in both tasks. In addition, a higher deceleration magnitude and a shorter acceleration for the CS+ as compared to the CS- were found in aversive but not in appetitive conditioning. There were medium-size correlations between aversive and appetitive CRs for subjective ratings and none for physiological responses. The results suggest similarities between cardiac response patterns in aversive and appetitive conditioning, which implies that bradycardia in conditioning might not be fear-specific but presents a valence-independent CS-elicited bradycardia.

Bradyarrhythmias in patients with SARS-CoV-2 infection: A narrative review and a clinical report.

Several cardiovascular diseases and arrhythmic disorders have been described in COVID-19 era as likely related to SARS-CoV-2 infection. The prognostic relevance of bradyarrhythmias during the infection has not been yet described and no data are available about long-term heart conduction disorders. A review of literature concerning the association between hypokinetic arrhythmias and COVID-19 from January 2020 to February 2021 was performed. The key-words used for the research were: "sinus node disfunction," "sick sinus syndrome (SSS)," "sino-atrial block," "atrio-ventricular block (AVB)," "bradyarrhythmias," and "COVID-19″ or "SARS-CoV-2.″ Excluding "relative bradycardia," a total of 38 cases of bradyarrhythmia related to SARS-CoV-2 infection have been described, even in very young people, requiring in many cases a definitive pacemaker implantation. Furthermore, we report a case of non-hospitalized 47-years old man with a SSS developed as a consequence of mild SARS-CoV-2 infection. While in all described cases heart conduction disorders were found at presentation of the infection or during hospitalization for COVID-19, in our case the diagnosis of SSS was made after the resolution of the infection. Although rarely, heart conduction disorders may occur during COVID-19 and the present case highlights that a cardiological follow up may be desirable even after the resolution of infection, especially in the presence of symptoms suggesting a possible heart involvement.

Contemporaneous Comparison of Outcomes Among Patients Implanted With a Leadless vs Transvenous Single-Chamber Ventricular Pacemaker.

Importance: The safety and efficacy of leadless VVI pacemakers have been demonstrated in multiple clinical trials, but the comparative performance of the device in a large, real-world population has not been examined. Objective: To compare patient characteristics and complications among patients implanted with leadless VVI and transvenous VVI pacemakers. Design, Setting, Participants: The Longitudinal Coverage With Evidence Development Study on Micra Leadless Pacemakers (Micra CED) is a continuously enrolling observational cohort study evaluating complications, utilization, and outcomes of leadless VVI pacemakers in the US Medicare fee-for-service population. Patients implanted between March 9, 2017, and December 1, 2018, were identified and included. All Medicare patients implanted with leadless VVI and transvenous VVI pacemakers during the study period were enrolled. Patients with less than 12 months of continuous enrollment in Medicare prior to leadless VVI or transvenous VVI implant and with evidence of a prior cardiovascular implantable electronic device were excluded, leaving 5746 patients with leadless VVI pacemakers and 9662 patients with transvenous VVI pacemakers. Data were analyzed from May 2018 to April 2021. Exposures: Medicare patients implanted with leadless VVI pacemakers or transvenous VVI pacemakers. Main Outcomes and Measures: The main outcomes were acute (30-day) complications and 6-month complications. Results: Of 15 408 patients, 6701 (43.5%) were female, and the mean (SD) age was 81.0 (8.7) years. Compared with patients with transvenous VVI pacemakers, patients with leadless VVI pacemakers were more likely to have end-stage kidney disease (690 [12.0%] vs 226 [2.3%]; P < .001) and a higher mean (SD) Charlson Comorbidity Index score (5.1 [3.4] vs 4.6 [3.0]; P < .001). The unadjusted acute complication rate was higher in patients with leadless VVI pacemakers relative to transvenous VVI pacemakers (484 of 5746 [8.4%] vs 707 of 9662 [7.3%]; P = .02). However, there was no significant difference in overall acute complication rates following adjustment for patient characteristics (7.7% vs 7.4%; risk difference, 0.3; 95% CI, -0.6 to 1.3; P = .49). Pericardial effusion and/or perforation within 30 days was significantly higher among patients with leadless VVI pacemakers compared with patients with transvenous VVI pacemakers in both unadjusted and adjusted models (unadjusted, 47 of 5746 [0.8%] vs 38 of 9662 [0.4%]; P < .001; adjusted, 0.8% vs 0.4%; risk difference, 0.4; 95% CI, 0.1 to 0.7; P = .004). Patients implanted with leadless VVI pacemakers had a lower rate of 6-month complications compared with patients implanted with transvenous VVI pacemakers (unadjusted hazard ratio, 0.84; 95% CI, 0.68-1.03; P = .10; adjusted hazard ratio, 0.77; 95% CI, 0.62-0.96; P = .02). Conclusions and Relevance: In this study, despite significant differences in patient characteristics, patients in whom a leadless pacemaker was implanted were observed to have higher rates of pericardial effusion and/or perforation but lower rates of other device-related complications and requirements for device revision at 6 months. Understanding the benefits and risks associated with leadless VVI pacemakers compared with transvenous VVI pacemakers can help clinicians and patients make informed treatment decisions.

Blood Pressure Control in Acute Stroke: Labetalol or Nicardipine?

PURPOSE: To assess the safety and efficacy of continuous infusion (CIV)-labetalol compared to -nicardipine in controlling blood pressure (BP) in the acute stroke setting. MATERIALS: Patients were eligible if they had a diagnosis of an acute stroke and were administered either CIV-labetalol or CIV-nicardipine. Study outcomes were assessed within the first 24 h of the antihypertensive infusion. RESULTS: A total of 3,093 patients were included with 3,008 patients in the CIV-nicardipine group and 85 in the CIV-labetalol group. No significant difference was observed in percent time at goal BP between the nicardipine (82%) and labetalol (85%) groups (p = 0.351). There was also no difference in BP variability between nicardipine (37%) and labetalol (39%) groups (p = 0.433). Labetalol was found to have a shorter time to goal BP as compared to nicardipine (24 min vs. 40 min; p = 0.021). While CIV-nicardipine did have a higher incidence of tachycardia compared to labetalol (17% vs. 4%; p <0.001), the incidence of hypotension (13% vs. 15%; p = 0.620) and bradycardia (24% vs. 22%; p = 0.797) were similar. CONCLUSIONS: These results indicate that CIV-labetalol and CIV-nicardipine are comparable in safety and efficacy in controlling BP for patients with acute stroke.

Ipsilateral somatic nerves mediate histamine-induced vasosensory reflex responses involving perivascular afferents in rat models.

Reflex cardiorespiratory alterations elicited after instillation of nociceptive agents intra-arterially (i.a) are termed as 'vasosensory reflex responses'. The present study was designed to evaluate such responses produced after i.a. instillation of histamine (1 mM; 10 mM; 100 mM) and to delineate the pathways i.e. the afferents and efferents mediating these responses. Blood pressure, electrocardiogram and respiratory excursions were recorded before and after injecting saline/histamine, in a local segment of femoral artery in urethane anesthetized rats. Paw edema and latencies of responses were also estimated. Separate groups of experiments were conducted to demonstrate the involvement of somatic nerves in mediating histamine-induced responses after ipsilateral femoral and sciatic nerve sectioning (+NX) and lignocaine pre-treatment (+Ligno). In addition, another set of experiments was performed after bilateral vagotomy (+VagX) and the responses after histamine instillation were studied. Histamine produced concentration-dependent hypotensive, bradycardiac, tachypnoeic and hyperventilatory responses of shorter latencies (2-7 s) favouring the neural mechanisms in eliciting the responses. Instillation of saline (time matched control) in a similar fashion produced no response, excluding the possibilities of ischemic/stretch effects. Paw edema was absent in both hind limbs indicating that the histamine did not reach the paws and did not spill out into the systemic circulation. +NX, +VagX, +Ligno attenuated histamine-induced cardiorespiratory responses significantly. These observations conclude that instillation of 10 mM of histamine produces optimal vasosensory reflex responses originating from the local vascular bed; afferents and efferents of which are mostly located in ipsilateral somatic and vagus nerves respectively.

Implementation of a practice plan for the outpatient cardiac evaluation of children after acute SARS-CoV-2 infection and a report of outcomes.

SARS-CoV-2 infection has been associated with cardiovascular disease in children, but which children need cardiac evaluation is unclear. We describe our experience evaluating 206 children for cardiac disease following SARS-CoV-2 infection (one of whom had ventricular ectopy) and propose a new guideline for management of these children. Routine cardiac screening after SARS-CoV-2 infection in children without any cardiac signs or symptoms does not appear to be high yield.

Relationship Between Intraoperative and Preoperative Ambulatory Nighttime Heart Rates: A Secondary Analysis of a Prospective Observational Study.

BACKGROUND: It remains unknown what constitutes physiologically relevant intraoperative bradycardia. Intraoperative bradycardia is usually defined using absolute heart rate thresholds, ignoring preoperative baseline heart rates. In contrast, we considered defining intraoperative bradycardia relative to preoperative ambulatory nighttime heart rate. Specifically, we hypothesized that the individual mean intraoperative heart rate is lower than the mean preoperative ambulatory nighttime heart rate. We, therefore, sought to investigate the relationship between the intraoperative and preoperative ambulatory nighttime heart rates in adults having noncardiac surgery with general anesthesia. Additionally, we sought to investigate the incidence of intraoperative bradycardia using relative versus absolute heart rate thresholds. METHODS: We conducted a secondary analysis of a database from a prospective study including preoperative ambulatory and intraoperative heart rates in 363 patients having noncardiac surgery with general anesthesia. RESULTS: The mean intraoperative heart rate was lower than the mean nighttime heart rate (mean difference, -9 bpm; 95% confidence interval [CI], -10 to -8 bpm; P < .001). The mean intraoperative heart rate was lower than the mean nighttime heart rate in 319 of 363 patients (88%; 95% CI, 84%-91%). The incidence of intraoperative bradycardia was 42% (95% CI, 38%-47%) when it was defined as intraoperative heart rate >30% lower than mean nighttime heart rate and 43% (95% CI, 38%-49%) when it was defined as intraoperative heart rate <45 bpm. CONCLUSIONS: The mean intraoperative heart rate is lower than the mean nighttime heart rate in about 9 of 10 patients. Intraoperative bradycardia might thus be physiologically and clinically important. Future research needs to investigate whether there is an association between intraoperative bradycardia and postoperative outcomes.

Symptomatic sinus bradycardia due to electrolyte imbalances in syndrome of inappropriate antidiuretic hormone (SIADH) related covid-19: a case report.

BACKGROUND: Coronavirus Disease-2019 (COVID-19) has been declared a global pandemic since March 11th, 2020. Despite emerging reports and literature covering a broad spectrum of COVID-19 clinical manifestations, facets of COVID-19 have not been fully elucidated. To the authors' concern, sinus bradycardia as a manifestation of COVID-19-induced syndrome of inappropriate antidiuretic hormone (SIADH) has never been reported before. CASE PRESENTATION: In this paper, we report a case of a 59-year-old male patient with confirmed COVID-19 initially presented with presyncope. Further investigations reveal sinus bradycardia related to COVID-19-induced SIADH. This case highlights the possibility of immuno-neuroendocrino-cardiovascular crosstalk resulting in an atypical manifestation of COVID-19: near syncope due to sinus bradycardia. CONCLUSIONS: Another possible cause of sinus bradycardia in COVID-19 is electrolyte imbalance due to COVID-19-related SIADH.

A Previously Healthy 18-Year-Old Male With Fever, Arrhythmia, and Shock.

A male individual aged 18 years with no significant past medical history presented with fever, headache, dry cough, and chest pain. On clinical examination, he had tachycardia and hypotension needing intravenous fluid resuscitation and inotropic support. A chest radiograph revealed streaky lung opacities, and he was treated with antibiotics for suspected community-acquired pneumonia complicated by septic shock. Significant elevation of cardiac enzymes was noted, and there was a continued need for inotropes to maintain normotension. He also developed intermittent bradycardia, with serial electrocardiograms showing first-degree atrioventricular block, low-voltage QRS complexes, and ST-T wave changes and telemetry demonstrating junctional and ventricular escape rhythm. A complete workup for sepsis and acute myocarditis were performed to find the etiologic agent. Intravenous immunoglobulins were started to treat myocarditis, with eventual clinical improvement. He was eventually diagnosed with an unusual etiology for his illness. He was noted to still have intermittent ventricular escape rhythm on electrocardiograms on follow-up 2 weeks after discharge but continues to remain asymptomatic and in good health.

Cigarette smoke exposure causes systemic and autonomic cardiocirculatory changes in rats depending on the daily exposure dose.

AIMS: To evaluate the systemic changes and autonomic cardiocirculatory control of awaken rats chronically exposed to the cigarette smoke (CS) of 1 or 2 cigarettes/day. MAIN METHODS: Rats were exposed to clean air (control) or cigarette smoke of 1 (CS1) or 2 (CS2) cigarettes/animal/day for 30 days. Then, arterial pressure (AP) and heart rate (HR) were recorded in conscious rats to assess spontaneous baroreflex sensitivity and HR and AP variabilities. Evoked baroreflex and cardiac autonomic tone were evaluated by vasoactive drugs and autonomic blockers, respectively. In another group, ventilatory and cardiovascular parameters were recorded under hypoxia and hypercapnia stimulus. At the end of protocols, heart, lung, kidneys and liver were collected for histological analysis. KEY FINDINGS: Rats exposed to CS showed morphological changes, being more evident in the CS2 group. Also, less weight gain and cardiac hypertrophy were prominent in CS2 rats. Basal AP and HR, spontaneous baroreflex sensitivity and cardiovascular variabilities were similar among groups. CS exposure progressively blunted the bradycardia response to phenylephrine (-2.2 ± 0.1 vs. -1.7 ± 0.2 vs. -1.5 ± 0.2) while the tachycardia response to sodium nitroprusside was slightly increased compared to control. Vagal tone was not affected by CS, but CS2 rats exhibited higher sympathetic tone (-25 ± 4 vs. -28 ± 4 vs. -56 ± 9) and lower intrinsic HR (411 ± 4 vs. 420 ± 8 vs. 390 ± 6). Exposure to CS of 2 cigarettes also exacerbated the reflex cardiovascular and ventilatory responses to hypoxia and hypercapnia. SIGNIFICANCE: CS exposure for 30 days promoted systemic changes and autonomic cardiocirculatory dysfunction in rats depending on the daily exposure dose.