However, this finding contrasts with work showing that less frequent drug use was associated with lower expenditure of money earned through participating in a job training program . An important distinction in our study: Providing a MA-negative sample yielded payment, whereas in the Subramaniam et al.’s study, participants earned money in an account at an hourly rate for work performed. In the present study, measured baseline decision-making tendencies were associated with future voucher spending during the CM trial. Specifically, a baseline tendency to favor frequent rewards was associated with a greater likelihood of voucher spending at the current visit after controlling for other confounding factors that could also impact spending at the current visit, including prior abstinence during the trial , prior wealth accrued during the trial , and baseline household income. This finding points to how individual differences in responding to reward frequency, measured using the IGT, link with spending in real life during a cash voucher-based CM program. Although a tendency to favor frequent rewards was related to future spending, this tendency was not also related to abstinence in our study. Only recent spending was related to future abstinence. This result could suggest that the decision-making process characterized by a prioritization of frequent reward outcomes may be related to abstinence,rolling benches but only indirectly, via recent spending. It may also be that the baseline decision-making process underlying the favorability of frequent rewards and spending happens to independently influence behaviors that support drug abstinence—influences that may be masked by our small sample size.
Future, fully powered research should aim to test these hypotheses further. In contrast, a baseline tendency to avoid immediate and large short-term rewards in favor of longer term gains was not associated with future spending but was associated with a greater likelihood of future abstinence. This finding may be because the preference for frequent rewards is associated with immediate spending, which reduces the opportunity for longer term spending. Despite the possible indirect role recent spending may have in explaining the relationship between an individualized tendency to favor frequent rewards and future abstinence, this is outweighed by the stronger relationship between prior abstinence and current abstinence. This finding is supported by several treatment studies that have demonstrated a link between baseline abstinence and future abstinence during treatment with respect to both methamphetamine and cocaine . However, given the confounding nature of the relationship between abstinence and spending embedded in the CM trial design, that is, one’s ability to spend cash vouchers is contingent on abstinence; the true extent of the relationship between decision-making in favor of frequent rewards and future abstinence via recent spending may in fact be under- or overestimated in this sample. Future study designs should look to decouple spending from abstinence to independently test such factors. There are several study limitations that should be identified. The small sample limits the generalizability of findings. Moreover, given that spending was conditional on abstinence, this led to a reduced sample size consisting only of the cases where a voucher was distributed , potentially biasing the sample toward participants who were able to achieve some degree of abstinence, and excluding those participants who were unable to achieve any abstinence.
Although this study has demonstrated how individual decision-making tendencies and spending may support abstinence, other factors including executive function capacity have also been shown to support sustained abstinence, demonstrated within the same CM pilot study . In summary, among participants with MUD, a baseline tendency to avoid short-term rewards in favor of larger long-term gains as well as recent spending were independently associated with abstinence reinforcement in a CM setting. Such findings highlight the importance of person-specific decision-making tendencies and spending in predicting the likelihood of achieving abstinence on CM, as well as providing an opportunity for cash voucher reinforcement programs to be individually tailored to maximize treatment success. Future work should further investigate the potential mechanistic role/s of decision-making tendencies and spending in promoting abstinence in cash voucher reinforcement treatment programs for individuals with substance use disorders.The effect of conventional tobacco cigarette smoking on the pathophysiology of coronary artery disease is relatively well defined; however, the effects on cardiac arrhythmia and proarrhythmic mechanism are less well understood. The situation has become more complex recently with the advent of modern tobacco products like electronic cigarettes and heated tobacco products , and the increased popularity of legalized marijuana,all of which are popularly assumed to be safer than tobacco cigarettes. Although non-conventional tobacco products and marijuana may represent an emerging threat to cardiovascular health,current knowledge regarding the mechanism by which smoking/vaping leads to cardiac arrhythmias remains limited.
An enhanced substrate for both atrial and ventricular arrhythmias has been shown to result from any combination of cardiac neural, electrical, and structural remodeling. Neural control of the heart, which involves both sympathetic and parasympathetic nerves, plays a vital role in the initiation and perpetuation of arrhythmia diseases due to its regulation of automaticity and triggered activity.Electrical remodeling refers to alterations in ion channels and connexins that promote the development of arrhythmias by affecting action potential duration and reentrant activity.10 Structural remodeling is an advanced process that progressively affects myocytes and the myocardial interstitium, resulting in myocyte hypertrophy, interstitial fibrosis, and cardiac chamber enlargement, and eventually promotes reentry.Previous studies have suggested that conventional tobacco smoking can lead to the imbalance of cardiac autonomic control by causing sympathetic over-innervation and parasympathetic withdrawal.A recent study revealed that e-cigs can also promote the imbalance of cardiac automatic control and further the inducibility of ventricular tachycardia Nicotine-mediated fibrosis and the activation of nicotinic acetylcholine receptor are considered to be the common proarrhythmogenic substrate caused by all nicotine-containing products.However, the increased risk of arrhythmias caused by non-nicotine products such as marijuana suggests unexpected effects that cannot be fully explained by nicotine. The impacts of chronic smoking and vaping of this wide range of tobacco and marijuana products on the formation of arrhythmogenic substrate, including cardiac neural, electrical, and structural remodeling, have not been fully determined. The overall goal of this study was to test the hypothesis that smoking/vaping these tobacco products or marijuana may increase the susceptibility to inducible tachycardia including atrial fibrillation andVT comparably to smoking conventional tobacco cigarettes, and to investigate potentially related cardiac electro-pathophysiologic modifications.Sprague-Dawley rats, 8–10 weeks old, of both genders, were used for this study. Group sizes varied from 5–16 depending on the experiment; a situation resulting from complications of the COVID-19 lab shutdowns although sufficient power was still achieved for an α of 0.05, two-tailed testing,rolling bench and power of 0.8 . Animal procedures were approved and monitored by the Institutional Animal Care and Use Committee of the University of California, San Francisco. The research reported in this paper adhered to the ARRIVE guidelines for reporting animal research and the National Academies of Sciences, Engineering, and Medicine Guide for the Care and Use of Laboratory Animals.To mimic human active smoking/vaping, conscious rats in restrainers were exposed to pulsatile smoke/aerosol commencing after at least 3 days of acclimation to the restrainers, by which time the rats tolerated being held, as determined by breathing smoothly and not struggling. Each rat was exposed 5 days/week for 2 months, one session/ day, with each session consisting of 10 cycles spread over 5 min, to approximate the consumption of a single cigarette or a single vaping session.Two out of 18 initial animals in the tobacco cigarette group died on days 1 and 14 of exposure and were replaced; no other mortalities occurred. Rats were exposed to one of the following products: Marlboro Red tobacco cigarettes , HTPs , e-cigs , marijuana, or “Placebo marijuana” . All required federal, state, and institutional approvals for acquisition and possession of marijuana and exposure of rodents were obtained.Air exposure was used as control. Group size was 8–16. Systolic blood pressure , echocardiography, ECG telemetry, arrhythmia inducibility testing, and optical mapping were assayed during or after exposure as described previously .
We measured conscious SBP by tail cuff on the first exposure day and at the end of the 2nd, 4th, 6th, and 8th week to determine progressively chronic effects. On each measurement day, SBP was measured twice, both before and after that day’s single exposure, to determine that day’s acute effect. Eight weeks post exposure, ex vivo heart optical mapping was performed as described previously to test the susceptibility to arrhythmias originating from left and right atria and ventricles and to evaluate their electrophysiological characteristics.The APD at 80% repolarization and calcium transient duration at 80% repolarization were measured after a series of 20×S1 pacing trains at the pacing cycle lengths of 150, 130, 120, 110,100, 90, 80, and 70 ms. The effective refractory period and the susceptibility to both AF and VT were tested via programmed stimulations including extra-stimuli and overdrive pacing. AF was diagnosed as fast and irregular beating lasting more than 2 seconds, whereas VT was determined as at least 6 non-driven consecutive ventricular premature beats.For histological analysis, hearts were weighed, fixed, and embedded in O.C.T compound for the following histological analyses.Heart coronal or transverse cryosections were stained with Sirius red/fast green to assess fibrosis or fluorescently stained for the assessment of the intrinsic cardiac nervous system and cardiac microvessels. ICNS as the autonomic nerve system inside the heart is vital for cardiac function and maintenance of normal heart rhythm.To visualize ICNS, we performed immunofluorescence staining for sympathetic and parasympathetic nerves. In order to quantify microvessels including capillaries and small precapillary arterioles with a cross area of 10–314 μm2 , slides were incubated with biotinylated Griffonia simplicifolia I lectin and then labeled with Alexa Fluor 488 Streptavidin as we previously described.Microvessel density and area percentage were calculated. Ten views were taken randomly from subepicardium, midmural, and subendocardium for each section to calculate mean optical area that represented the average intensity level using Fiji ImageJ.Most procedures were analyzed by a blinded investigator. Some functional measurements were partially blinded due to contstraints imposed by the pandemic lab shutdowns . To determine whether exposure to tobacco and marijuana smoke/aerosol affected cardiac function, we performed echocardiography. As shown in Fig. 2, exposure for 8 weeks progressively reduced both ejection fraction and fractional area change in all non-air groups compared to their baseline levels. Left ventricular end-systolic volume and end-diastolic volume were gradually increased in non-air groups; by 8 weeks post-exposure, LVESV and LVEDV were enlarged significantly in all non-air groups compared to baseline , along with an increase in LV mass compared to baseline and to Air group . Moreover, exposure to all conditions except air resulted in an enlargement of left atrial diameter by the 4th week of exposure and the enlargement continued to increase through the 8th week. These findings suggest that exposure to tobacco and marijuana products led to reduced LV function and enlarged cardiac chambers, indicating LV dysfunction and remodeling associated with smoking/vaping.All of the normal-to-normal RR intervals of all conditions superimposed in Supplementary Fig.1 showed the same RR intervals distribution pattern in the form of a Poincaré plot, which plots each pair of RR intervals between 2 consecutive beats and thus quantifies the distribution pattern of heart rate mapping. Data in Fig. 3A indicated only exposure to JUUL led to a shortened average NN interval. Surprisingly, chronic exposure to smoke of CIG, IQOS, MJ, and pb-MJ did not shorten the NN interval and actually prolonged it. Using a time domain method to directly evaluate the degree of dispersion of NN interval revealed that exposure to tobacco and marijuana products compared to Air caused a significant reduction of the overall HRV indicators , including the average of 2 mins standard deviation of NN intervals , the root mean square of successive differences between normal heartbeats , the number of pairs of successive NN intervals that differ by more than 9 ms , and the proportion of NN9 divided by the total number of NN intervals , which suggests a depressed parasympathetic function. Frequency domain method for HRV analysis, an indirect method to reflect sympathetic and parasympathetic function, showed that all of these products decreased the overall HRV, especially the sympathetic modulations . Compared to Air, most of conditions had a lower total power , very-low frequency band , and lower levels of low frequency band , ratio of low/high frequency . Both LF and HF were depressed by IQOS exposure but apparently HF was influenced more and that caused an increased LF/HF value.